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4,712 results on '"Medicinal Chemistry"'

1. Hit 'em where it hurts: The growing and structurally diverse family of peptides that target lipid-II

Author

Sub Membrane Biochemistry & Biophysics, Sub Medicinal Chemistry & Chemical biol., Membrane Biochemistry and Biophysics, Medicinal Chemistry, Medicinal Chemistry and Chemical Biology, Oppedijk, Sabine F., Martin, Nathaniel I., Breukink, Eefjan, Sub Membrane Biochemistry & Biophysics, Sub Medicinal Chemistry & Chemical biol., Membrane Biochemistry and Biophysics, Medicinal Chemistry, Medicinal Chemistry and Chemical Biology, Oppedijk, Sabine F., Martin, Nathaniel I., and Breukink, Eefjan

Published
2016

2. Liquid chromatography-tandem mass spectrometric assay for ponatinib and N-desmethyl ponatinib in mouse plasma

Author

Sub Medicinal Chemistry & Chemical biol., Sub Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Medicinal Chemistry and Chemical Biology, Sparidans, Rolf W, Kort, Anita, Schinkel, Alfred H, Schellens, Jan H M, Beijnen, Jos H, Sub Medicinal Chemistry & Chemical biol., Sub Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Medicinal Chemistry and Chemical Biology, Sparidans, Rolf W, Kort, Anita, Schinkel, Alfred H, Schellens, Jan H M, and Beijnen, Jos H

Published
2016

3. Liquid chromatography-tandem mass spectrometric assay for the simultaneous determination of the irreversible BTK inhibitor ibrutinib and its dihydrodiol-metabolite in plasma and its application in mouse pharmacokinetic studies

Author

Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Medicinal Chemistry and Chemical Biology, Pharmacoepidemiology and Clinical Pharmacology, Rood, Johannes J M, van Hoppe, Stephanie, Schinkel, Alfred H., Schellens, Jan H M, Beijnen, Jos H., Sparidans, Rolf W., Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Medicinal Chemistry and Chemical Biology, Pharmacoepidemiology and Clinical Pharmacology, Rood, Johannes J M, van Hoppe, Stephanie, Schinkel, Alfred H., Schellens, Jan H M, Beijnen, Jos H., and Sparidans, Rolf W.

Published
2016

4. Stability of individual LPS-induced ex vivo cytokine release in a whole blood assay over a five-year interval

Author

LS IRAS VPH VV (veterinaire volksgezh.), One Health Chemisch, One Health Microbieel, dIRAS RA-I&I RA, dIRAS RA-2, Dep IRAS, Sub Medicinal Chemistry & Chemical biol., Spierenburg, E A J, Portengen, L, Smit, L A M, Krop, E J M, Hylkema, M N, Rijkers, G T, Heederik, D, Wouters, I M, LS IRAS VPH VV (veterinaire volksgezh.), One Health Chemisch, One Health Microbieel, dIRAS RA-I&I RA, dIRAS RA-2, Dep IRAS, Sub Medicinal Chemistry & Chemical biol., Spierenburg, E A J, Portengen, L, Smit, L A M, Krop, E J M, Hylkema, M N, Rijkers, G T, Heederik, D, and Wouters, I M

Published
2018

5. Liposome functionalization with copper-free 'click chemistry'

Author

Sub Drug delivery, UIPS - Utrecht Institute for Pharmaceutical Sciences, Sub Medicinal Chemistry & Chemical biol., Pharmaceutics, Medicinal Chemistry and Chemical Biology, Oude Blenke, Erik, Klaasse, Gruson, Merten, Hannes, Plückthun, Andreas, Mastrobattista, Enrico, Martin, Nathaniel I., Sub Drug delivery, UIPS - Utrecht Institute for Pharmaceutical Sciences, Sub Medicinal Chemistry & Chemical biol., Pharmaceutics, Medicinal Chemistry and Chemical Biology, Oude Blenke, Erik, Klaasse, Gruson, Merten, Hannes, Plückthun, Andreas, Mastrobattista, Enrico, and Martin, Nathaniel I.

Published
2015

6. Improving the biological activity of the antimicrobial peptide anoplin by membrane anchoring through a lipophilic amino acid derivative

Author

Medicinal Chemistry and Chemical Biology, Membrane Biochemistry and Biophysics, Sub Medicinal Chemistry & Chemical biol., Sub Biochemistry of Membranes begr1-6-12, Sub Membrane Biochemistry & Biophysics, Sub Medicinal Chemistry begr. 01-01-2014, Slootweg, J.C., van Schaik, T.B., Quarles van Ufford, H.C., Breukink, E.J., Liskamp, R.M.J., Rijkers, D.T.S., Medicinal Chemistry and Chemical Biology, Membrane Biochemistry and Biophysics, Sub Medicinal Chemistry & Chemical biol., Sub Biochemistry of Membranes begr1-6-12, Sub Membrane Biochemistry & Biophysics, Sub Medicinal Chemistry begr. 01-01-2014, Slootweg, J.C., van Schaik, T.B., Quarles van Ufford, H.C., Breukink, E.J., Liskamp, R.M.J., and Rijkers, D.T.S.

Published
2013

7. The N-terminal fragment of human islet amyloid polypeptide is non-fibrillogenic in the presence of membranes and does not cause leakage of bilayers of physiologically relevant lipid composition

Author

Biochemistry of membranes, Medicinal Chemistry and Chemical Biology, SYNTHESE, Sub Biochemistry of Membranes begr1-6-12, Dep Farmaceutische wetenschappen, Sub Medicinal Chemistry begr. 01-01-2014, Sub Medicinal Chemistry & Chemical biol., Khemtemourian, L.P., Engel, M.F.M., Liskamp, R.M.J., Höppener, J.W.M., Killian, J.A., Biochemistry of membranes, Medicinal Chemistry and Chemical Biology, SYNTHESE, Sub Biochemistry of Membranes begr1-6-12, Dep Farmaceutische wetenschappen, Sub Medicinal Chemistry begr. 01-01-2014, Sub Medicinal Chemistry & Chemical biol., Khemtemourian, L.P., Engel, M.F.M., Liskamp, R.M.J., Höppener, J.W.M., and Killian, J.A.

Published
2010

8. Potential scorpionate antibiotics: targeted hydrolysis of lipid II containing model membranes by vancomycin-TACzyme conjugates and modulation of their antibacterial activity by Zn-ions

Author

Biochemie van Membranen, Biochemistry of membranes, Chemical Biology & Organic Chemistry, Medicinal Chemistry, SYNTHESE, Dep Farmaceutische wetenschappen, Dep Scheikunde, Sub Algemeen Scheikunde, Sub Medicinal Chemistry begr. 01-01-2014, Albada, H.B., Arnusch, C.J., Branderhorst, H.M., Verel, A.M., Janssen, W.T.M., Breukink, E.J., de Kruijff, B., Pieters, R.J., Liskamp, R.M.J., Biochemie van Membranen, Biochemistry of membranes, Chemical Biology & Organic Chemistry, Medicinal Chemistry, SYNTHESE, Dep Farmaceutische wetenschappen, Dep Scheikunde, Sub Algemeen Scheikunde, Sub Medicinal Chemistry begr. 01-01-2014, Albada, H.B., Arnusch, C.J., Branderhorst, H.M., Verel, A.M., Janssen, W.T.M., Breukink, E.J., de Kruijff, B., Pieters, R.J., and Liskamp, R.M.J.

Published
2009

9. Erratum: Corrigendum to “Assessing the oral bioavailability of difluorosialic acid prodrugs, potent viral neuraminidase inhibitors, using a snapshot PK screening assay” (Bioorg. Med. Chem. Lett. (2015) 25 (2505–2509))

Author

Sub Chemical pharmacology, Department of Chemistry, Medicinal Chemistry and Chemical Biology, Arns, Steve, Tan, Jason, Sun, Sharon, Galey, Adam, Zisman, Natalia, Ross, Fiona, Udechukwu, Jenna, Dercho, Samantha, Gusti, Vionarica, Paquette, Jay, Wennekes, Tom, Webb, Murray, Bourque, Elyse, Withers, Stephen G., Liggins, Richard, Sub Chemical pharmacology, Department of Chemistry, Medicinal Chemistry and Chemical Biology, Arns, Steve, Tan, Jason, Sun, Sharon, Galey, Adam, Zisman, Natalia, Ross, Fiona, Udechukwu, Jenna, Dercho, Samantha, Gusti, Vionarica, Paquette, Jay, Wennekes, Tom, Webb, Murray, Bourque, Elyse, Withers, Stephen G., and Liggins, Richard

Published
2016

11. Recent developments in the chromatographic bioanalysis of approved kinase inhibitor drugs in oncology

Author

Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Pharmacoepidemiology and Clinical Pharmacology, Rood, Johannes J M, Schellens, Jan H M, Beijnen, Jos H, Sparidans, Rolf W, Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Pharmacoepidemiology and Clinical Pharmacology, Rood, Johannes J M, Schellens, Jan H M, Beijnen, Jos H, and Sparidans, Rolf W

Published
2016

12. Liquid chromatography-tandem mass spectrometric assay for therapeutic drug monitoring of the B-Raf inhibitor encorafenib, the EGFR inhibitors afatinib, erlotinib and gefitinib and the O-desmethyl metabolites of erlotinib and gefitinib in human plasma

Author

Sub Medicinal Chemistry & Chemical biol., Sub Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Sparidans, Rolf W, Rosing, Hilde, Rood, Johannes J M, Schellens, Jan H M, Beijnen, Jos H, Sub Medicinal Chemistry & Chemical biol., Sub Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Sparidans, Rolf W, Rosing, Hilde, Rood, Johannes J M, Schellens, Jan H M, and Beijnen, Jos H

Published
2016

13. Liquid chromatography-tandem mass spectrometric assay for the T790M mutant EGFR inhibitor osimertinib (AZD9291) in human plasma

Author

Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Pharmacoepidemiology and Clinical Pharmacology, Rood, Johannes J M, van Bussel, Mark T J, Schellens, Jan H M, Beijnen, Jos H, Sparidans, Rolf W, Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Pharmacoepidemiology and Clinical Pharmacology, Rood, Johannes J M, van Bussel, Mark T J, Schellens, Jan H M, Beijnen, Jos H, and Sparidans, Rolf W

Published
2016

14. Synthesis and evaluation of locostatin-based chemical probes towards PEBP-proteins

Author

Sub Chemical pharmacology, Medicinal Chemistry and Chemical Biology, Hoogenboom, Jorin, Fiers, Martijn, Immink, Richard, Zuilhof, Han, Wennekes, Tom, Sub Chemical pharmacology, Medicinal Chemistry and Chemical Biology, Hoogenboom, Jorin, Fiers, Martijn, Immink, Richard, Zuilhof, Han, and Wennekes, Tom

Published
2016

15. Multiple pathway assessment to predict anti-atherogenic efficacy of drugs targeting macrophages in atherosclerotic plaques

Author

Sub General Pharmaceutics, Sub Medicinal Chemistry & Chemical biol., Sub Drug targeting, Pharmaceutics, Alaarg, Amr, Kang, He Zheng, van der Valk, Fleur M, da Silva, Acarilia Eduardo, Versloot, Miranda, Quarles Van Ufford, Linda, Schulte, Dominik M, Storm, G, Metselaar, Josbert M, Stroes, Erik S G, Hamers, Anouk A J, Sub General Pharmaceutics, Sub Medicinal Chemistry & Chemical biol., Sub Drug targeting, Pharmaceutics, Alaarg, Amr, Kang, He Zheng, van der Valk, Fleur M, da Silva, Acarilia Eduardo, Versloot, Miranda, Quarles Van Ufford, Linda, Schulte, Dominik M, Storm, G, Metselaar, Josbert M, Stroes, Erik S G, and Hamers, Anouk A J

Published
2016

17. Corrigendum to “Assessing the oral bioavailability of difluorosialic acid prodrugs, potent viral neuraminidase inhibitors, using a snapshot PK screening assay” [Bioorg. Med. Chem. Lett. 25 (2015) 2505–2509]

Author

Sub Chemical pharmacology, Department of Chemistry, Medicinal Chemistry and Chemical Biology, Arns, Steve, Tan, Jason, Sun, Sharon, Galey, Adam, Zisman, Natalia, Ross, Fiona, Udechukwu, Jenna, Dercho, Samantha, Gusti, Vionarica, Paquette, Jay, Wennekes, Tom, Webb, Murray, Bourque, Elyse, Withers, Stephen G., Liggins, Richard, Sub Chemical pharmacology, Department of Chemistry, Medicinal Chemistry and Chemical Biology, Arns, Steve, Tan, Jason, Sun, Sharon, Galey, Adam, Zisman, Natalia, Ross, Fiona, Udechukwu, Jenna, Dercho, Samantha, Gusti, Vionarica, Paquette, Jay, Wennekes, Tom, Webb, Murray, Bourque, Elyse, Withers, Stephen G., and Liggins, Richard

Published
2016

18. Liquid chromatography-tandem mass spectrometric assay for the T790M mutant EGFR inhibitor osimertinib (AZD9291) in human plasma

Author

Pharmacoepidemiology and Clinical Pharmacology, Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Rood, Johannes J M, van Bussel, Mark T J, Schellens, Jan H M, Beijnen, Jos H, Sparidans, Rolf W, Pharmacoepidemiology and Clinical Pharmacology, Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Rood, Johannes J M, van Bussel, Mark T J, Schellens, Jan H M, Beijnen, Jos H, and Sparidans, Rolf W

Published
2016

19. Tumor localizing agents. IX. Radioiodinated cholesterol

Author

Laboratory of Medicinal Chemistry, College of Pharmacy and Department of Internal Medicine (Nuclear Medicine), The University of Michigan, Ann Arbor, Michigan 48104, USA, no department foundLaboratory of Medicinal Chemistry, College of Pharmacy and Department of Internal Medicine (Nuclear Medicine), The University of Michigan, Ann Arbor, Michigan 48104, USA, Counsell, Raymond E., Ranade, Vasant V., Blair, R. J., Beierwaltes, William H., Weinhold, Paul A., Laboratory of Medicinal Chemistry, College of Pharmacy and Department of Internal Medicine (Nuclear Medicine), The University of Michigan, Ann Arbor, Michigan 48104, USA, no department foundLaboratory of Medicinal Chemistry, College of Pharmacy and Department of Internal Medicine (Nuclear Medicine), The University of Michigan, Ann Arbor, Michigan 48104, USA, Counsell, Raymond E., Ranade, Vasant V., Blair, R. J., Beierwaltes, William H., and Weinhold, Paul A.

Abstract

19-Iodocholesterol-125I was synthesized for study as a possible agent for photoscanning the adrenal gland and associated tumors. In contrast to previous radioiodinated steroids, it was found to be much less prone to rapid in vivo deiodination. Preliminary tissue distribution studies and biochemical analyses have revealed a marked similarity in the behavior of the radioiodinated derivative with the natural steroid. The concentration of radioactivity in the adrenal cortex of dogs at 48 hours was found to greatly exceed that found in other organs.

Published
2006

20. Synthesis of 1-(2-aminopropyl)benzimidazoles, structurally related to the TIBO derivative R82150, with activity against human immunodeficiency virus.

Author

Department of Chemistry, College of Literature, Sciences, and Arts, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109, USA, Department of Medicinal Chemistry, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109, USA, Department of Biologic and Material Sciences, School of Dentistry, The University of Michigan, Ann Arbor, Michigan 48109, USA, Department of Chemistry, College of Literature, Sciences, and Arts, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Medicinal Chemistry, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109, USA., Department of Microbiology and Immunology, Bowman Gray School of Medicine, Winston-Salem, NC 27157, USA, Microbiology Research Department, Southern Research Institute, Birmingham, AL 35205, USA, Swayze, Eric E., Peiris, Sithumini M., Kucera, Louis S., White, E. Lucile, Wise, Dean S., Drach, John C., Townsend, Leroy B., Department of Chemistry, College of Literature, Sciences, and Arts, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109, USA, Department of Medicinal Chemistry, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109, USA, Department of Biologic and Material Sciences, School of Dentistry, The University of Michigan, Ann Arbor, Michigan 48109, USA, Department of Chemistry, College of Literature, Sciences, and Arts, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Medicinal Chemistry, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109, USA., Department of Microbiology and Immunology, Bowman Gray School of Medicine, Winston-Salem, NC 27157, USA, Microbiology Research Department, Southern Research Institute, Birmingham, AL 35205, USA, Swayze, Eric E., Peiris, Sithumini M., Kucera, Louis S., White, E. Lucile, Wise, Dean S., Drach, John C., and Townsend, Leroy B.

Abstract

A number of 1-(2-aminopropyl)-2-mercaptobenzimidazoles related to the TIBO derivatives R82150 have been prepared and tested for their activity against human immunodeficiency virus type 1 (HIV-1). These compounds were all modest inhibitors of the cytophatic effects of HIV-1 in vitro, but only very weak inhibitors of HIV-1 reverse transcriptase (RT).A number of 1-(2-aminopropyl)-2-mercaptobenzimidazole derivatives related to the TIBO derivative R82150 have been prepared and tested for their activity against human immunodeficiency virus type 1 (HIV-1). These compounds are all modest inhibitors of the cytopathic effects of HIV-1 in vitro, but were only weak inhibitors of HIV-1 reverse transcriptase (RT).

Published
2006

21. Selective localization of radioiodinated alkylphosphocholine derivatives in tumors

Author

Department of Pharmacology, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Internal Medicine, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Pharmacology, The University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Division of Nuclear Medicine, VA Medical Center, Ann Arbor, MI 48109, U.S.A., Plotzke, Kathleen P., Haradahira, Terushi, Stancato, Louis F., Olken, Norman M., Skinner, Scott, Gross, Milton D., Wahl, Richard L., Counsell, Raymond E., Department of Pharmacology, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Internal Medicine, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Pharmacology, The University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Division of Nuclear Medicine, VA Medical Center, Ann Arbor, MI 48109, U.S.A., Plotzke, Kathleen P., Haradahira, Terushi, Stancato, Louis F., Olken, Norman M., Skinner, Scott, Gross, Milton D., Wahl, Richard L., and Counsell, Raymond E.

Abstract

We have designed and synthesized two radioiodinated analogs of hexadecylphosphocholine in order to evaluate their tumor imaging potential. 12-(m[125I]iodophenyl)dodecyl phosphocholine (NM-324) and hexadecyl-2-[N, N-dimethyl-N-(m[125I]iodobenzyl-ammonium]ethyl phosphate (NM-326) demonstrated the ability of such compounds to localize in and thereby visualize the Walker 256 tumor in rats. However, the tumor avidity of NM-324 was far superior to NM-326. In addition, NM-324 showed excellent tumor localization in athymic mice bearing subcutaneous human tumors.

Published
2006

22. Design, synthesis and activity against human cytomegalovirus of non-phosphorylatable analogs of toyocamycin, sangivamycin and thiosangivamycin

Author

Interdepartamental Program in Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Department of Biologic and Material Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Department of Chemistry, College of Literature, Arts and Sciences, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A.; Interdepartamental Program in Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Renau, Thomas E., Ludwig, Mary S., Drach, John C., Townsend, Leroy B., Interdepartamental Program in Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Department of Biologic and Material Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Department of Chemistry, College of Literature, Arts and Sciences, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A.; Interdepartamental Program in Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Renau, Thomas E., Ludwig, Mary S., Drach, John C., and Townsend, Leroy B.

Abstract

A number of 7-alkyl 4-aminopyrrolo[2,3-pyrimidine derivatives related to toyocamycin, sangivamycin and thiosangivamycin have been prepared and tested for their activity against human cytomegalovirus (HCMV). Only the thioamide substituted derivatives demonstrated biological activity.

Published
2006

23. Synthesis of potential antiprogestogens

Author

Department of Medical Pharmacology, University of Uppsala, Uppsala, Sweden; Laboratory of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48104, U.S.A., Laboratory of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48104, U.S.A.; Department of Medical Pharmacology, University of Uppsala, Uppsala, Sweden, Beyer, Bernardo, Terenius, Lars, Brueggemeier, Robert W., Ranade, Vasant V., Counsell, Raymond E., Department of Medical Pharmacology, University of Uppsala, Uppsala, Sweden; Laboratory of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48104, U.S.A., Laboratory of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48104, U.S.A.; Department of Medical Pharmacology, University of Uppsala, Uppsala, Sweden, Beyer, Bernardo, Terenius, Lars, Brueggemeier, Robert W., Ranade, Vasant V., and Counsell, Raymond E.

Abstract

Acylated derivatives of 17[alpha]-hydroxyprogesterone were prepared in order to test the hypothesis that dialkylamino alkyl moieties have the effect of transforming progestogens into antiprogestogens. This approach has been successful with certain estrogens. Compounds with other functional groups were synthesized to determine whether these might exert binding influence outside the area occupied by progesterone itself. The compounds were tested for competitive affinity against tritiated progesterone and receptor from rabbit uterus cytosol. The low affinity of all derivatives makes it unlikely that they would be active as antiprogestational agents.

Published
2006

24. A convenient solid phase synthesis of S-palmitoyl transmembrane peptides

Author

Biochemie van Membranen, Medicinal Chemistry van immunologische en neurologische ziekteprocessen, SYNTHESE, Medicinal Chemistry, Dep Farmaceutische wetenschappen, Dep Scheikunde, Rijkers, D.T.S., Kruijtzer, J.A.W., Killian, J.A., Liskamp, R.M.J., Biochemie van Membranen, Medicinal Chemistry van immunologische en neurologische ziekteprocessen, SYNTHESE, Medicinal Chemistry, Dep Farmaceutische wetenschappen, Dep Scheikunde, Rijkers, D.T.S., Kruijtzer, J.A.W., Killian, J.A., and Liskamp, R.M.J.

Published
2005

25. Stabilization of peptide guinea pig myelin basic protein 72-85 by N-terminal acetylation-implications for immunological studies

Author

Biokatalyse, Medicinal Chemistry van immunologische en neurologische ziekteprocessen, Medicinal Chemistry, Faculteit Diergeneeskunde, Dep Farmaceutische wetenschappen, Dep Scheikunde, Haan, E., Wauben, M.H.M., Wagenaar-Hilbers, J.P.A., Grosfeld, M.C., Rijkers, D.T.S., Moret, E.E., Liskamp, R.M.J., Biokatalyse, Medicinal Chemistry van immunologische en neurologische ziekteprocessen, Medicinal Chemistry, Faculteit Diergeneeskunde, Dep Farmaceutische wetenschappen, Dep Scheikunde, Haan, E., Wauben, M.H.M., Wagenaar-Hilbers, J.P.A., Grosfeld, M.C., Rijkers, D.T.S., Moret, E.E., and Liskamp, R.M.J.

Published
2004

26. Analysis of caffeine and paraxanthine in human saliva with ultra-high-performance liquid chromatography for CYP1A2 phenotyping

Author

Sub Biomolecular analysis, Sub Onderwijsinstituut Farmacie, Medicinal Chemistry and Chemical Biology, Jordan, Nan Yeun, Mimpen, Jolet Y., van den Bogaard, Willie J. M., Flesch, Frits M., van de Meent, Michiel H. M., Torano, Javier Sastre, Sub Biomolecular analysis, Sub Onderwijsinstituut Farmacie, Medicinal Chemistry and Chemical Biology, Jordan, Nan Yeun, Mimpen, Jolet Y., van den Bogaard, Willie J. M., Flesch, Frits M., van de Meent, Michiel H. M., and Torano, Javier Sastre

Published
2015

27. Liquid chromatography-tandem mass spectrometric assay for the PI3K/mTOR inhibitor GSK2126458 in mouse plasma and tumor homogenate

Author

Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Molecular Pharmacy, Pharmacoepidemiology and Clinical Pharmacology, Dolman, M. Emmy M, Westerhout, Ellen M., Hamdi, Mohamed, Schellens, Jan H M, Beijnen, Jos H., Sparidans, Rolf W., Sub Clinical Pharmacology, Sub Medicinal Chemistry & Chemical biol., Molecular Pharmacy, Pharmacoepidemiology and Clinical Pharmacology, Dolman, M. Emmy M, Westerhout, Ellen M., Hamdi, Mohamed, Schellens, Jan H M, Beijnen, Jos H., and Sparidans, Rolf W.

Published
2015

28. Assignment of hexuronic acid stereochemistry in synthetic heparan sulfate tetrasaccharides with 2-O-sulfo uronic acids using electron detachment dissociation

Author

Medicinal Chemistry and Chemical Biology, Sub General Molecular Pharmacy, Agyekum, Isaac, Patel, Anish B., Zong, Chengli, Boons, Geert Jan, Amster, I. Jonathan, Medicinal Chemistry and Chemical Biology, Sub General Molecular Pharmacy, Agyekum, Isaac, Patel, Anish B., Zong, Chengli, Boons, Geert Jan, and Amster, I. Jonathan

Published
2015

30. Semi-synthesis of biologically active nisin hybrids composed of the native lanthionine ABC-fragment and a cross-stapled synthetic DE-fragment

Author

Sub Medicinal Chemistry & Chemical biol., Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Molecular Pharmacy, Slootweg, Jack C., Peters, Nienke, Quarles Van Ufford, H. C., Breukink, Eefjan, Liskamp, Rob M J, Rijkers, Dirk T S, Sub Medicinal Chemistry & Chemical biol., Sub Membrane Biochemistry & Biophysics, Membrane Biochemistry and Biophysics, Molecular Pharmacy, Slootweg, Jack C., Peters, Nienke, Quarles Van Ufford, H. C., Breukink, Eefjan, Liskamp, Rob M J, and Rijkers, Dirk T S

Published
2014

31. Photocrosslinking and click chemistry enable the specific detection of proteins interacting with phospholipids at the membrane interface

Author

Biomolecular Mass Spectrometry and Proteomics, Massaspectrometrie, Membrane Enzymology, SYNTHESE, Dep Farmaceutische wetenschappen, Sub Algemeen Scheikunde, Sub Medicinal Chemistry begr. 01-01-2014, Sub Membrane Enzymology begr. 01-06-12, Gubbens, J., Ruijter, E., Fays, L.E.V., Damen, J.M.A., de Kruijff, B., Slijper, M., Rijkers, D.T.S., Liskamp, R.M.J., de Kroon, A.I.P.M., Biomolecular Mass Spectrometry and Proteomics, Massaspectrometrie, Membrane Enzymology, SYNTHESE, Dep Farmaceutische wetenschappen, Sub Algemeen Scheikunde, Sub Medicinal Chemistry begr. 01-01-2014, Sub Membrane Enzymology begr. 01-06-12, Gubbens, J., Ruijter, E., Fays, L.E.V., Damen, J.M.A., de Kruijff, B., Slijper, M., Rijkers, D.T.S., Liskamp, R.M.J., and de Kroon, A.I.P.M.

Published
2009

32. Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis

Author

Afd Chemical Biology and Drug Discovery, Dep Farmaceutische wetenschappen, Medicinal Chemistry, Brouwer, Arwin J., Elgersma, Ronald C., Jagodzinska, Monika, Rijkers, Dirk T.S., Liskamp, Rob M.J., Afd Chemical Biology and Drug Discovery, Dep Farmaceutische wetenschappen, Medicinal Chemistry, Brouwer, Arwin J., Elgersma, Ronald C., Jagodzinska, Monika, Rijkers, Dirk T.S., and Liskamp, Rob M.J.

Published
2008

33. Tumor localizing agents V. Radioiodinated pregnanes

Author

Laboratory of Medicinal Chemistry, College of Pharmacy The University of Michigan, Ann Arbor, Michigan 48104, USA, Counsell, Raymond E., Hong, B. H., Willette, R. E., Ranade, Vasant V., Laboratory of Medicinal Chemistry, College of Pharmacy The University of Michigan, Ann Arbor, Michigan 48104, USA, Counsell, Raymond E., Hong, B. H., Willette, R. E., and Ranade, Vasant V.

Abstract

Previous studies with progesterone-4-14C suggested that a radioiodinated analog might be useful for photoscanning the adrenal gland and associated tumors. 21-Iodoprogesterone was prepared by conversion of deoxycorticosterone to its mesylate and subsequent displacement with iodide. Depending on the conditions for mesylation, 21-chloroprogesterone could also be isolated. 21-Iodopregnenolone acetate was obtained in a similar manner from the 21-bromo analog which in turn was prepared in good yield from the enol acetate of pregnenolone acetate. The radioiodinated steroids were prepared by isotope exchange with sodium iodide-125 in refluxing acetone. Tissue distribution studies showed that the radioactivity concentrated mainly in the thyroid gland presumably as a result of rapid in vivo deiodination.

Published
2006

34. Interaction of [-Pen2, -Pen5]enkephalin and [-Ala2, Glu4]deltorphin with [delta]-opioid receptor subtypes in vivo

Author

College of Pharmacy, University of Michigan, Ann Arbor, MI, USA, eltorphin II in mice: evidence for delta receptor subtypes., Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA, Department of Chemistry, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA, Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA, Vanderah, Todd, Takemori, A.E., Sultana, M., Portoghese, P.S., Mosberg, Henry I., Hruby, V.J., Haaseth, R.C., Matsunaga, T.O., Porreca, Frank, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA, eltorphin II in mice: evidence for delta receptor subtypes., Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA, Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA, Department of Chemistry, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA, Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA, Vanderah, Todd, Takemori, A.E., Sultana, M., Portoghese, P.S., Mosberg, Henry I., Hruby, V.J., Haaseth, R.C., Matsunaga, T.O., and Porreca, Frank

Abstract

The interaction of [-Pen2, -Pen5]enkephalin (DPDPE) and [-Ala2, Glu4]deltorphin with [delta]-opioid receptor subtypes was investigated. Pretreatment of mice with the [delta]1-opioid receptor antagonists, [-Ala2, Leu5, Cys6]enkephalin (DALCE), produced a virtually complete antagonism of the antinociceptive actions of DPDPE, but had no effect on those of [-Ala2, Glu4]deltorphin. In DALCE pretreated mice (i.e., [delta]1-opioid receptors blocked), DPDPE was able to significantly antagonize the antinociceptive effects of [-Ala2, Glu4]deltorphin. Pretreatment of mice with the [delta]2-opioid receptor antagonist, na naltrindole-5'-isothiocynate (5'-NTII) produced a virtually complete antagonism of the antinociceptive effects of [-Ala2, Glu4]deltorphin, but had no effect on the antinociception produced by DPDPE. In 5'-NTII pretreated mice (i.e., [delta]2-opioid receptors blocked), [-Ala2, Glu4]deltorphin had no effect on the antinociception produced by DPDPE. These data suggest that [-Ala2, Glu4]deltorphin is highly selective for the [delta]2-opioid receptor in vivo, and that neither agonist nor antagonist actions can be demonstrated at [delta]1-opioid receptors for this peptide. In contrast, under appropriate conditions, DPDPE can be shown to interact with both [delta]1- and [delta]2-opioid receptor subtypes; DPDPE may have limited efficacy (i.e., is a partial agonist) at the [delta]2-opioid receptor.

Published
2006

35. Relationship between cytotoxicity and conversion of thiosangivamycin analogs to toyocamycin analogs in cell culture medium

Author

Interdepartmental Graduate Program in Medicinal Chemistry, College of Pharmacy, U.S.A.;Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, U.S.A., Renau, Thomas E., Lee, James S., Kim, Hanna, Young, Christopher G., Wotring, Linda L., Townsend, Leroy B., Drach, John C., Interdepartmental Graduate Program in Medicinal Chemistry, College of Pharmacy, U.S.A.;Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109-1078, U.S.A., Renau, Thomas E., Lee, James S., Kim, Hanna, Young, Christopher G., Wotring, Linda L., Townsend, Leroy B., and Drach, John C.

Abstract

Non-nucleoside analogs of the pyrrolopyrimidine nucleosides toyocamycin, sangivamycin and thiosangivamycin have been synthesized and their cytotoxicity in mammalian cells determined. While studying the effects of 5-thioamide-substituted analogs on cell growth, we observed an interesting phenomenon in which cells recovered spontaneously from growth inhibition during extended incubations. HPLC studies demonstrated that the 5-thioamide moiety of several structurally dissimilar 7-substituted 4-aminopyrrolo[2,3-d]pyrimidines, including thiosangivamycin, is unstable in cell culture medium and is converted to the corresponding 5-nitrile with a half-life of approximately 48 hr. In contrast, different substituents at the 4-position of the heterocycle significantly affected the stability of the 5-thioamide moiety. Conversion of the thioamide to the nitrile was caused by components in the cell culture medium, not components of serum. The above observations demonstrate that caution should be exercised in interpreting biological data obtained in vitro for 5-thioamide pyrrolo(2,3-d]pyrimidines.

Published
2006

36. A comparison of proteins and peptides as substrates for microsomal and solubilized oligosaccharyltransferase

Author

Department of Chemistry and Interdepartmental Program in Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1055, U.S.A., Liu, Yun-Li, Hoops, Geoffrey C., Coward, James K., Department of Chemistry and Interdepartmental Program in Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1055, U.S.A., Liu, Yun-Li, Hoops, Geoffrey C., and Coward, James K.

Abstract

A chemoenzymatic synthesis of homogeneous neoglycoproteins and glycopeptides was explored using oligosaccharyltransferase isolated from yeast. Neither the microsomal form nor the solubilized form of the enzyme catalyzed the transfer of the core Glc3Man9(GlcNAc)2 oligosaccharide to chemically modified ribonuclease A or [alpha]-lactalbumin. Similarly, no transfer was observed to the 32-amino acid peptide hormone, calcitonin, by either the membrane-bound or soluble form of oligosaccharyltransferase. However, a 17-amino acid fragment of yeast invertase with the unusual sequence containing two overlapping glycosylation sequons proved to be a good substrate, slightly less effective than the well studied tripeptide, Bz-Asn-Leu-Thr-NH2. Product analysis using gel permeation chromatography showed that the expected glycopeptides were formed and endo H-catalyzed cleavage of the oligosaccharide portion from the glycopeptides demonstrated that the glycopeptides contained the same carbohydrate moiety.

Published
2006

37. The synthesis of DL-3,3-Difluoroglutamic acid from a 3-oxoprolinol derivative

Author

Department of Chemistry and Interdepartmental Program in Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1055 U.S.A., Hart, Barry P., Coward, James K., Department of Chemistry and Interdepartmental Program in Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1055 U.S.A., Hart, Barry P., and Coward, James K.

Abstract

DL-3,3-Difluoroglutamic acid was synthesized from a masked 3-hydroxyprolinol, 6-hydroxy-1-aza-3-oxabicyclo[3.3.0]octan-2-one, in eight steps. The described synthetic route expands the utility of fluoroproline derivatives as precursors of fluoroglutamic acids.

Published
2006

38. Comparison of methods for incorporating a radioiodinated residualizing cholesteryl ester analog into low density lipoprotein

Author

Interdepartmental Program in Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Pharmacology, Ann Arbor, MI 48105, U.S.A., Parke-Davis Pharm. Res. Div., Warner-Lambert Co., Ann Arbor, MI 48105, U.S.A., DeForge, Laura E., Degalan, Mark R., Ruyan, Mohamed K., Newton, Roger S., Counsell, Raymond E., Interdepartmental Program in Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Pharmacology, Ann Arbor, MI 48105, U.S.A., Parke-Davis Pharm. Res. Div., Warner-Lambert Co., Ann Arbor, MI 48105, U.S.A., DeForge, Laura E., Degalan, Mark R., Ruyan, Mohamed K., Newton, Roger S., and Counsell, Raymond E.

Abstract

Two different methods were evaluated for incorporating [125I]cholesteryl iopanoate ([125I]CI), a non-hydrolyzable cholesteryl ester analog, into LDL. The first procedure was an organic solvent delipidation-reconstitution procedure (R[125I-CI]LDL) while the second involved incubation of detergent (Tween-20)-solubilized [125I]CI with whole plasma (D[125I-CI]LDL). R[125I-CI]LDL behaved similar to native LDL in vitro, but was markedly different in vivo, apparently due to a heterogeneity in particle size. D[125I-CI]LDL, however, was metabolized normally both in vitro and in vivo. These results, combined with the residualizing nature of [125I]CI, demonstrate that D[125I-CI]LDL is appropriate for tracing LDL uptake in vivo.

Published
2006

39. Interaction of fatty acids with recombinant rat intestinal and liver fatty acid-binding proteins

Author

Department of Pathology and Laboratory Medicine and Howard Hughes Medical Institute, Medical Center, University of Michigan, Ann Arbor, Michigan 48105, USA, Division of Pharmacology and Medicinal Chemistry, Department of Pharmacology and Cell Biophysics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0004, USA, Nemecz, Gyorgy, Hubbell, Timothy, Jefferson, John R., Lowe, John B., Schroeder, Friedhelm, Department of Pathology and Laboratory Medicine and Howard Hughes Medical Institute, Medical Center, University of Michigan, Ann Arbor, Michigan 48105, USA, Division of Pharmacology and Medicinal Chemistry, Department of Pharmacology and Cell Biophysics, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0004, USA, Nemecz, Gyorgy, Hubbell, Timothy, Jefferson, John R., Lowe, John B., and Schroeder, Friedhelm

Abstract

Intestinal enterocytes contain two homologous fatty acid-binding proteins, intestinal fatty acid-binding protein (I-FABP)2 and liver fatty acid-binding protein (L-FABP). Since the functional basis for this multiplicity is not known, the fatty acid-binding specificity of recombinant forms of both rat I-FABP and rat L-FABP was examined. A systematic comparative analysis of the 18 carbon chain length fatty acid binding parameters, using both radiolabeled (stearic, oleic, and linoleic) and fluorescent (trans-parinaric and cis-parinaric) fatty acids, was undertaken. Results obtained with a classical Lipidex-1000 binding assay, which requires separation of bound from free fatty acid, were confirmed with a fluorescent fatty acid-binding assay not requiring separation of bound and unbound ligand. Depending on the nature of the fatty acid ligand, I-FABP bound fatty acid had dissociation constants between 0.2 and 3.1 [mu] and a consistent 1:1 molar ratio. The dissociation constants for L-FABP bound fatty acids ranged between 0.9 and 2.6 [mu] and the protein bound up to 2 mol fatty acid per mole of protein. Both fatty acid-binding proteins exhibited relatively higher affinity for unsaturated fatty acids as compared to saturated fatty acids of the same chain length. cis-Parinaric acid or trans-parinaric acid (each containing four double bonds) bound to L-FABP and I-FABP were displaced in a competitive manner by nonfluorescent fatty acid. Hill plots of the binding of cis- and trans- parinaric acid to L-FABP showed that the binding affinities of the two sites were very similar and did not exhibit cooperativity. The lack of fluorescence self-quenching upon binding 2 mol of either trans- or cis- parinaric acid/mol L-FABP is consistent with the presence of two binding sites with dissimilar orientation in the L-FABP. Thus, the difference in binding capacity between I-FABP and L-FABP predicts a structurally different binding site or sites.

Published
2006

40. Synthesis of a pyrido[1,2-a]purine nucleoside by a novel ring cleavage-annulation reaction of 3-[beta]-D-ribofuranosylimidazo-[4,5-d]--triazin-4-one

Author

Department of Medicinal Chemistry, College of Pharmacy and Department of Chemistry, College of Literature, Science, and Arts; University of Michigan, Ann Arbor, Michigan 48109 U.S.A., Krawczyk, Steven H., Townsend, Leroy B., Department of Medicinal Chemistry, College of Pharmacy and Department of Chemistry, College of Literature, Science, and Arts; University of Michigan, Ann Arbor, Michigan 48109 U.S.A., Krawczyk, Steven H., and Townsend, Leroy B.

Abstract

Treatment of 7-(2,3,5-tris--(t-butyldimethylsilyl)-[beta]--ribofuranosyl)imidazo[4,5-]-v-triazin-4-one (1) with MnO2 in hot pyridine furnished 7-(2,3,5-tris--(t-butyldimethylsilyl)-[beta]--ribofuranosyl)pyrido[1,2-a]-purine (4). Treatment of 4 with tetra--butylammonium fluoride furnished the free nucleoside 5.

Published
2006

41. A new and novel approach towards the synthesis of 3'-deoxy-3'-hydroxymethyl ribofuosides

Author

Department of Chemistry, College of Literature, Science, and Arts and Department of Medicinal Chemistry, College of Pharmacy University of Michigan, Ann Arbor, Michigan, 48109 U.S.A., Pudlo, Jeffrey S., Townsend, Leroy B., Department of Chemistry, College of Literature, Science, and Arts and Department of Medicinal Chemistry, College of Pharmacy University of Michigan, Ann Arbor, Michigan, 48109 U.S.A., Pudlo, Jeffrey S., and Townsend, Leroy B.

Abstract

The synthesis of 1,2,5 tri--benzoyl-3-deoxy-3-[(benzyloxy)methyl]-[alpha], gb-D-ribofuranose () from 1,2 --isopropylidene-[alpha]-D-xylofuranose () has been achieved in an overall yield of 37%. Compound is a properly substituted intermediate for the synthesis of novel 3'-"branched" nucleoside analogs.

Published
2006

42. The synthesis and chemistry of certain anthelmintic benzimidazoles

Author

Department of Medicinal Chemistry, College of Pharmacy and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA, Townsend, Leroy B., Wise, Dean S., Department of Medicinal Chemistry, College of Pharmacy and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA, Townsend, Leroy B., and Wise, Dean S.

Abstract

A basis for interest in the benzimidazole ring system as a nucleus from which to develop potential chemotherapeutic agents was established in the 1950s when it was found that 5,6-dimethyl-l-([alpha]-D-ribofuranosyl)benzimidazole (I) was an integral part of the structure of vitamin B12. As a result of these interests and extensive studies, one health related arena that has benefited greatly has been the treatment of parasitic diseases. The discovery of thiabendazole in 1961 further spurred chemists around the world to design and synthesize several thousand benzimidazoles for screening for anthelmintic activity but less than twenty of them have reached commercial use. Much of this work has been done by pharmaceutical companies and is only reported in the patent literature. In this paper, Leroy Townsend and Dean Wise review the development of some of the synthetic methods that have been critical to the preparation of the benzimidazoles of anthelmintic importance. Only a few molecules that demonstrate the processes are discussed here, but numerous reviews of the synthesis and chemistry of other benzimidazoles are available1-3.

Published
2006

43. Interaction of, -erythro- and, -threo-[gamma]-fluoromethotrexate with human leukemia cell dihydrofolate reductase

Author

Departments of Chemistry and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, U.S.A., Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, NY 14263, USA, McGuire, John J., Haile, William H., Coward, James K., Departments of Chemistry and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, U.S.A., Grace Cancer Drug Center, Roswell Park Memorial Institute, Buffalo, NY 14263, USA, McGuire, John J., Haile, William H., and Coward, James K.

Abstract

Gamma-fluoromethotrexate (FMTX) is a poorly glutamylated mimic of the anti-cancer drug methotrexate (MTX) which is useful in studies of the roles of MTX poly-[gamma]-glutamates. A second chiral center occurs at C-4 of the 4-fluoroglutamate used to synthesize FMTX and, as a consequence, FMTX occurs as both, -erythro and, -threo diastereomers. The interaction of both diastereomers with intracellular dihydrofolate reductase has been examined in the human leukemia cell line CCRF-CEM, using a centrifugal column technique. Measurements of the rate at which radiolabel was displaced from [3H]MTX-saturated dihydrofolate reductase following suspension of the cells in unlabeled drug indicated that MTX and the erythro isomer of FMTX gave essentially the same rate of displacement; the rate of displacement by the threo isomer of FMTX was slower, but the interpretation of these data was ambiguous since the rate of transport of threo-FMTX may have been limiting. In reciprocal experiments in which dihydrofolate reductase was saturated with [3H]erythro-FMTX, the erythro isomer and MTX again behaved equivalently in terms of displacement. When dihydrofolate reductase was saturated with [3H]threo-FMTX, the radiolabel was clearly displaced at a much faster rate than either other radiolabel regardless of whether the displacing agent was MTX or the isomer. These results indicate a distinct stereospecificity for interaction of inhibitor with dihydrofolate reductase in which the threo isomer has a faster off-rate. Of the two FMTX diastereomers, the erythro isomer thus most closely mimics the properties of MTX.

Published
2006

44. Assignment of the chemical shift values of N-trityl -homoserine lactone

Author

Department of Medicinal Chemistry and Phamacognosy College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Son, Jong-Keun, Kalvin, Douglas M., Woodard, Ronald W., Department of Medicinal Chemistry and Phamacognosy College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Son, Jong-Keun, Kalvin, Douglas M., and Woodard, Ronald W.

Abstract

This paper reports the correct assignment of all chemical shift values of N-trityl -homoserine lactone based on the 1H-nmr spectra of N-trityl-2S, 3R-[3-2H]- and 2S, 3S-[2,3-2H2]homoserine lactone.

Published
2006

45. A practical large scale chemical synthesis of chiral glycines

Author

Department of Medicinal Chemistry, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A, Ramalingam, Kondareddiar, Nanjappan, Palaniappagownder, Kalvin, Douglas M., Woodard, Ronald W., Department of Medicinal Chemistry, College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A, Ramalingam, Kondareddiar, Nanjappan, Palaniappagownder, Kalvin, Douglas M., and Woodard, Ronald W.

Abstract

(R)- and (S)-[2-2H]glycine of high chiral purity were synthesized in large quantities in [approximate] 40% overall yield from readily available starting materials via a totally chemical procedure. Reduction of either [1-2H]-furfural or [1-2H]-4-methoxybenzaldehyde with either (+) or ( - )-B-isopinocampheyl-9-borabicyclo[3.3.1]nonane gave chiral arylmethyl alcohols which were converted into their respective phthaloyl amino derivatives of the opposite configuration at the methylene carbon via the Mitsunobu reaction. The aromatic groups were oxidatively unmasked to give their corresponding glycine derivatives by either ozone or ruthenium tetraoxide oxidation.

Published
2006

46. A rapid and sensitive screening method for the detection of anti-2-acetylaminofluorene immunoglobulins

Author

Department of Pathology, Biochemistry Section, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Warner Lambert Corporation, 2800 Plymouth Road, Ann Arbor, MI 48105, U.S.A., Silbart, Lawrence K., Nordblom, Gerald D., Keren, David F., Wise, Jr., Dean S., Lincoln, Pamela M., Townsend, Leroy B., Department of Pathology, Biochemistry Section, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Warner Lambert Corporation, 2800 Plymouth Road, Ann Arbor, MI 48105, U.S.A., Silbart, Lawrence K., Nordblom, Gerald D., Keren, David F., Wise, Jr., Dean S., Lincoln, Pamela M., and Townsend, Leroy B.

Abstract

A method is described in which anti-2-acetylaminofluorene immunoglobulins may be detected using a simple and sensitive screening procedure. The method is based on immunoglobulin binding of an 125I derivatized 2-aminofluorene radiotracer. Tracer binding is not isotype specific, and thus the method is useful for the detection of either IgG or IgA. Competitive binding experiments with the radiotracer were used to determine the specificity of immunoglobulin response by measurement of cross-reactivity with related ligands. This method allows quantitation of the immune response to the carcinogen in serum and other biological fluids (i.e., intestinal secretions).

Published
2006

47. Specificity of adenine binding to lima bean lectin

Author

Departments of Biological Chemistry and Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Roberts, David D., Arjunan, Palanisamy, Townsend, Leroy B., Goldstein, Irwin J., Departments of Biological Chemistry and Medicinal Chemistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Roberts, David D., Arjunan, Palanisamy, Townsend, Leroy B., and Goldstein, Irwin J.

Abstract

The interactions between lima bean lectin (LBL) and adenine were examined using a series of synthetic purine analogs. Binding was sensitive to modification at most positions of the purine ring, suggesting a high degree of specificity for adenine binding. Methylation ofthe 6 NH2-group to MeNH-, Me2N- and Me3N+-analogs progressively decreased the binding affinity. Compounds lacking the 6 NH2-group were not bound. Methylation of adenine at N1, N3 or N7 also inhibited binding, indicating specific interactions with these ring nitrogens. In contrast to the previous report that N9-substituted adenines, nucleosides and nucleotides were not bound [Roberts, D.D. and Goldstein, I.J. (1983) J. Biol. Chem. 258, 13820], 9-methyl- and 9-benzyl-substituted adenines were bound to LBL with high affinity. Substitutions at C-2 and C-8 were tolerated and, in some cases, increased the affinity of binding to LBL. Heterotropic interactions between the adenine and 1,8-anilinonaphthalenesulphonate binding sites were also sensitive to modification of the purine ring. 2-Methylthioadenine and 4-aminopyrazolo[3,4-d]pyrimidine showed increased allosteric interaction with 1,8-anilinonaphthalenesulphonate binding, whereas several adenine analogs with a 9-p-nitrobenzyl substituent appeared to be negative effectors of 1,8-anilinonaphthalenesulphonate binding.

Published
2006

48. Radioiodination via isotope exchange in pivalic acid

Author

Departments of Medicinal Chemistry and Pharmacology, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Weichert, Jamey P., Van Dort, Marcian E., Groziak, Michael P., Counsell, Raymond E., Departments of Medicinal Chemistry and Pharmacology, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Weichert, Jamey P., Van Dort, Marcian E., Groziak, Michael P., and Counsell, Raymond E.

Abstract

A variety of benzoic and aryl aliphatic mono and polyiodinated acids and esters (sterol, triglyceride) were radioiodinated in 55-99% radiochemical yield by isotope exchange with Na 125I in a melt of pivalic acid. In general, the reaction was complete in 1 h at 155[deg]C with little or no substrate decompostion. High specific activity studies afforded 125I-labeled iopanoic acid with a specific activity of over 700 Ci/mmol.

Published
2006

49. Selective inhibition of herpes simplex virus ribonucleoside diphosphate reductase by derivatives of 2-acetylpyridine thiosemicarbazone

Author

Interdepartmental Graduate Program in Medicinal Chemistry and Department of Oral Biology, School of Dentistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Turk, Steven R., Shipman, Charles Jr., Drach, John C., Interdepartmental Graduate Program in Medicinal Chemistry and Department of Oral Biology, School of Dentistry, The University of Michigan, Ann Arbor, MI 48109, U.S.A., Turk, Steven R., Shipman, Charles Jr., and Drach, John C.

Abstract

The effects of thiosemicarbazone derivatives of 2-acetylpyridine on mammalian and viral ribonucleoside diphosphate reductases were investigated. The enzymes were partially purified from uninfected and herpes simplex virus type-1 (HSV-1)-infected KB cells by sequential salt fractionation with streptomycin sulfate and ammonium sulfate and by affinity chromatography on ATP-agarose. The five thiosemicarbazone derivatives investigated were all potent inhibitors of the virus-induced reductase. Fifty percent inhibitory concentrations (50 values) range from 2 to 13 [mu]M. Four of the five derivatives also were inhibitors of the host cell reductase . A semicarbazone was inactive against the cellular enzyme and relatively weak as an inhibitor of the viral enzyme . Four of the six compounds were preferential inhibitors of the viral reductase based on a comparison of 50 values (5- to> 85-fold difference). Kinetic experiments revealed that inhibition of the HSV-1 reductase by the thiosemicarbazones was noncompetitive with respect to CDP and dithiothreitol. A comparison of the inhibitory effects of 2-acetylpyridine thiosemicarbazone itself on viral reductase and on virus replication in vitro demonstrated a similarity in the dose-response relationships for the two parameters. This observation supports the hypothesis that the HSV-induced ribonucleoside diphosphate reductase is an important target for the design of antiviral drugs.

Published
2006

50. A convenient synthesis of -(5'-deoxy-5'-adenosyl)- (+/- ) -2-methylhomocysteine

Author

Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Ramalingam, Kondareddiar, Woodard, Ronald W., Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065 U.S.A., Ramalingam, Kondareddiar, and Woodard, Ronald W.

Abstract

The synthesis of -(5'-deoxy-5'-adenosyl)-+-2-methylhomocysteine in two steps from +--2-methylmethionine is described.

Published
2006

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