15 results on '"Wahajul Haq"'
Search Results
2. Synthesis and Antimalarial Activity of 4‑Methylaminoquinoline Compounds against Drug-Resistant Parasite
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Vinay Shankar Tiwari, Prince Joshi, Kanchan Yadav, Anamika Sharma, Sushobhan Chowdhury, Ashan Manhas, Niti Kumar, Renu Tripathi, and Wahajul Haq
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Chemistry ,QD1-999 - Published
- 2021
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3. A facile and chemoselectivity in synthesis of 4-chloro-N-(4-((1-hydroxy-2-methylpropan-2-yl)oxy)phenethyl)benzamide, the alcohol derivative of Bezafibrate
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Greesha N. Majethia, Wahajul Haq, and Ganesaratnam K. Balendiran
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Bezafibrate ,Chemoselectivity ,Reduction of carboxylic acid ,Sodium borohydride ,Mixed anhydride ,Chemistry ,QD1-999 - Abstract
A facile method for the reduction of carboxylic acid group of Bezafibrate, an approved drug, is described. The selective reduction of carboxylic acid group to corresponding alcohol was carried out by activation of the carboxylic acid moiety via mixed anhydride followed by the addition of stoichiometric amount of NaBH4 and methanol to obtain the first alcohol variant of Bezafibrate. The reaction was completed in 5–10 min in excellent yield and purity. The new alcohol derivative was characterized by spectroscopic methods. This is the first report on this new molecule.
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- 2022
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4. Direct physical interaction of active Ras with mSIN1 regulates mTORC2 signaling
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Mehraj-U-Din Lone, Javed Miyan, Mohammad Asif, Showkat A. Malik, Parul Dubey, Varsha Singh, Kavita Singh, Kalyan Mitra, Deepali Pandey, Wahajul Haq, Himanshi Amita, Prince Kumar Singh, Wieland Kiess, Franziska Kaessner, Antje Garten, and Smrati Bhadauria
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Cancer ,Mammalian target of rapamycin (mTOR) ,Signaling ,Ras ,Superoxide anion ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The mechanistic (or mammalian) target of rapamycin (mTOR), a Ser/Thr kinase, associates with different subunits forming two functionally distinct complexes, mTORC1 and mTORC2, regulating a diverse set of cellular functions in response to growth factors, cellular energy levels, and nutrients. The mechanisms regulating mTORC1 activity are well characterized; regulation of mTORC2 activity, however, remains obscure. While studies conducted in Dictyostelium suggest a possible role of Ras protein as a potential upstream regulator of mTORC2, definitive studies delineating the underlying molecular mechanisms, particularly in mammalian cells, are still lacking. Methods Protein levels were measured by Western blotting and kinase activity of mTORC2 was analyzed by in vitro kinase assay. In situ Proximity ligation assay (PLA) and co-immunoprecipitation assay was performed to detect protein-protein interaction. Protein localization was investigated by immunofluorescence and subcellular fractionation while cellular function of mTORC2 was assessed by assaying extent of cell migration and invasion. Results Here, we present experimental evidence in support of the role of Ras activation as an upstream regulatory switch governing mTORC2 signaling in mammalian cancer cells. We report that active Ras through its interaction with mSIN1 accounts for mTORC2 activation, while disruption of this interaction by genetic means or via peptide-based competitive hindrance, impedes mTORC2 signaling. Conclusions Our study defines the regulatory role played by Ras during mTORC2 signaling in mammalian cells and highlights the importance of Ras-mSIN1 interaction in the assembly of functionally intact mTORC2.
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- 2019
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5. Fibrane the reduced derivative of fenofibrate
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Amanda E. Kotheimer, Wahajul Haq, and Ganesaratnam K. Balendiran
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Fibrate ,Fibrane ,Chemistry ,QD1-999 - Abstract
Synthetic routes for the preparation of (i) isopropyl 2-(4-(4-chlorobenzyl)phenoxy)-2-methyl propanoate (Reduced Fenofibrate, Fibrane) (2) from isopropyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate (Fenofibrate) (1) in a single step is established in good yield and purity under mild conditions. The newly synthesized derivative of Fenofibrate has been characterized by NMR and IR spectroscopy techniques. Selective conversion of biphenyl ketone moiety, in the presence of ester carbonyl group in Fenofibrate to its corresponding alkane can be performed by Pd catalyst reduction with hydrogen transfer agent ammonium formate.
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- 2020
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6. Immunogenicity and Protective Efficacy of T-Cell Epitopes Derived From Potential Th1 Stimulatory Proteins of Leishmania (Leishmania) donovani
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Sumit Joshi, Narendra Kumar Yadav, Keerti Rawat, Vikash Kumar, Rafat Ali, Amogh Anant Sahasrabuddhe, Mohammad Imran Siddiqi, Wahajul Haq, Shyam Sundar, and Anuradha Dube
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visceral leishmaniasis ,Th1 stimulatory proteins ,immunoinformatics ,T-cell epitopes ,peptides ,human PBMCs ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Development of a suitable vaccine against visceral leishmaniasis (VL), a fatal parasitic disease, is considered to be vital for maintaining the success of kala-azar control programs. The fact that Leishmania-infected individuals generate life-long immunity offers a viable proposition in this direction. Our prior studies demonstrated that T-helper1 (Th1) type of cellular response was generated by six potential recombinant proteins viz. elongation factor-2 (elF-2), enolase, aldolase, triose phosphate isomerase (TPI), protein disulfide isomerase (PDI) and p45, derived from a soluble antigenic fraction (89.9–97.1 kDa) of Leishmania (Leishmania) donovani promastigote, in treated Leishmania patients and golden hamsters and showed significant prophylactic potential against experimental VL. Moreover, since, it is well-known that our immune system, in general, triggers production of specific protective immunity in response to a small number of amino acids (peptide), this led to the identification of antigenic epitopes of the above-stated proteins utilizing immunoinformatics. Out of thirty-six, three peptides-P-10 (enolase), P-14, and P-15 (TPI) elicited common significant lymphoproliferative as well as Th1-biased cytokine responses both in golden hamsters and human subjects. Further, immunization with these peptides plus BCG offered 75% prophylactic efficacy with boosted cellular immune response in golden hamsters against Leishmania challenge which is indicative of their candidature as potential vaccine candidates.
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- 2019
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7. Combination of liposomal CpG oligodeoxynucleotide 2006 and miltefosine induces strong cell-mediated immunity during experimental visceral leishmaniasis.
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Rahul Shivahare, Preeti Vishwakarma, Naveen Parmar, Pawan Kumar Yadav, Wahajul Haq, Mrigank Srivastava, Suman Gupta, and Susanta Kar
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Medicine ,Science - Abstract
Immuno-modulators in combination with antileishmanial drug miltefosine is a better therapeutic approach for treatment of Visceral Leishmaniasis (VL) as it not only reduces the dose of miltefosine but also shortens the treatment regimen. However, immunological mechanisms behind the perceived benefits of this combination therapy have not been investigated in detail. In the present study, we hypothesized that potential use of drugs that target the host in addition to the parasite might represent an alternative strategy for combination therapy. We investigated immune responses generated in Leishmania donovani infected animals (hamsters and mice) treated with combination of CpG-ODN-2006 and miltefosine at short dose regimen. Infected animals were administered CpG-ODN-2006 (0.4 mg/kg, single dose), as free and liposomal form, either alone or in combination with miltefosine for 5 consecutive days and parasite clearance was evaluated at day 4 and 7 post treatment. Animals that received liposomal CpG-ODN-2006 (lipo-CpG-ODN-2006) and sub-curative miltefosine (5 mg/kg) showed the best inhibition of parasite multiplication (∼97%) which was associated with a biased Th1 immune response in. Moreover, compared to all the other treated groups, we observed increased mRNA expression levels of pro-inflammatory cytokines (IFN-γ, TNF-α and IL-12) and significantly suppressed levels of Th2 cytokines (IL-10 and TGF-β) on day 4 post treatment in animals that underwent combination therapy with lipo-CpG-ODN-2006 and sub-curative miltefosine. Additionally, same therapy also induced heightened iNOS mRNA levels and NO generation, increased IgG2 antibody level and strong T-cell response in these hamsters compared with all the other treated groups. Collectively, our results suggest that combination of lipo-CpG-ODN-2006 and sub-curative miltefosine generates protective T-cell response in an animal model of visceral leishmaniasis which is characterized by strong Th1 biased immune response thereby underlining our hypothesis that combination therapy, at short dose regimen can be used as a novel way of treating visceral leishmaniasis.
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- 2014
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8. Human beta casein fragment (54-59) modulates M. bovis BCG survival and basic transcription factor 3 (BTF3) expression in THP-1 cell line.
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Dharamsheela Thakur, Reshu Saxena, Vandana Singh, Wahajul Haq, S B Katti, Bhupendra Narain Singh, and Raj Kamal Tripathi
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Medicine ,Science - Abstract
Immunostimulatory peptides potentiate the immune system of the host and are being used as a viable adjunct to established therapeutic modalities in treatment of cancer and microbial infections. Several peptides derived from milk protein have been reported to induce immunostimulatory activity. Human β -casein fragment (54-59), natural sequence peptide (NS) carrying the Val-Glu-Pro-Ile-Pro-Tyr amino acid residues, was reported to activate the macrophages and impart potent immunostimulatory activity. In present study, we found that this peptide increases the clearance of M. bovis BCG from THP-1 cell line in vitro. The key biomolecules, involved in the clearance of BCG from macrophage like, nitric oxide, pro-inflammatory cytokines and chemokines, were not found to be significantly altered after peptide treatment in comparison to the untreated control. Using proteomic approach we found that BTF3a, an isoform of the Basic Transcription Factor, BTF3, was down regulated in THP-1 cell line after peptide treatment. This was reconfirmed by real time RT-PCR and western blotting. We report the BTF3a as a novel target of this hexapeptide. Based on the earlier findings and the results from the present studies, we suggest that the down regulation of BTF3a following the peptide treatment may augment the M. bovis BCG mediated apoptosis resulting in enhanced clearance of M. bovis BCG from THP-1 cell line.
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- 2012
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9. New acylides: synthesis of 3-O-[γ-(4-oxo-2-aryl-thiazolidin-3-yl)butyryl]erythromycin A derivatives
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Deepa Pandey, Wahajul Haq, and Seturam B. Katti
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Science ,Organic chemistry ,QD241-441 - Abstract
In search of new erythromycin derivatives 3-O-[γ-(4-oxo-2-aryl-thiazolidin-3-yl)butyryl]erythromycin A derivatives have been synthesized. The 3-hydroxy group was derivatised to a primary amine and subsequently the thiazolidinone nucleus was generated at the amino functionality through DCC mediated one-pot three-component reaction in good yields.
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- 2008
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10. Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice
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Chhitar M. Gupta, Kalaimathi Murugesan, Raghunandan Mahadeva, Wahajul Haq, and Padmapriya Srinivasan
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Pharmaceutical Science ,Peptide ,Apoptosis ,02 engineering and technology ,Pharmacology ,01 natural sciences ,Polyethylene Glycols ,chemistry.chemical_compound ,Mice ,International Journal of Nanomedicine ,Drug Discovery ,Spectroscopy, Fourier Transform Infrared ,palmitoyl-tuftsin ,Original Research ,antitumor ,chemistry.chemical_classification ,Liposome ,Drug Carriers ,General Medicine ,021001 nanoscience & nanotechnology ,Endocytosis ,Tuftsin ,lipids (amino acids, peptides, and proteins) ,0210 nano-technology ,Drug carrier ,medicine.drug ,Curcumin ,Drug Compounding ,Biophysics ,Bioengineering ,Antineoplastic Agents ,010402 general chemistry ,doxorubicin ,Ehrlich ascites carcinoma ,Biomaterials ,medicine ,Animals ,Humans ,Doxorubicin ,Particle Size ,Carcinoma, Ehrlich Tumor ,Cell Proliferation ,Organic Chemistry ,0104 chemical sciences ,Drug Liberation ,Kinetics ,chemistry ,HeLa Cells - Abstract
Kalaimathi Murugesan,1 Padmapriya Srinivasan,1,* Raghunandan Mahadeva,1,* Chhitar M Gupta,1 Wahajul Haq2 1Institute of Bioinformatics and Applied Biotechnology (IBAB), Bangalore, India; 2Central Drug Research Institute (CDRI), Medicinal and Process Chemistry Division, Lucknow, India*These authors contributed equally to this workCorrespondence: Kalaimathi MurugesanInstitute of Bioinformatics and Applied Biotechnology (IBAB), Biotech Park, Electronic City Phase I, Bangalore 560100, IndiaTel +919585986415Email mathi.biotech@gmail.comBackground: Targeted multidrug-loaded delivery systems have emerged as an advanced strategy for cancer treatment. In this context, antibodies, hormones, and small peptides have been coupled to the surface of drug carriers, such as liposomes, polymeric and metallic nanoparticles loaded with drugs, as tumor-specific ligands. In the present study, we have grafted a natural macrophage stimulating peptide, tuftsin, on the surface of the liposomes (LPs) that were loaded with doxorubicin (DOX) and/or curcumin (CUR), by attaching to its C-terminus a palmitoyl residue (Thr-Lys-Pro-Arg-CO-NH-(CH2)2-NH-COC15H31, P.Tuft) to enable its grafting within the liposome’s bilayer.Methods: The prepared drug-loaded liposomes (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft-LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs, P.Tuft-DOX-CUR LPs) were thoroughly characterised in terms of particle size, drug content, encapsulation efficiency and structural properties using UV–visible spectroscopy, dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR). The anti-cancer activity and drug toxicity of the liposomal formulations were examined on Ehrlich ascites carcinoma (EAC) tumor-induced mice model.Results: A significant reduction in the tumor weight and volume was observed upon treating the tumor-bearing mice with palmitoyl tuftsin-grafted dual drug-loaded liposomes (P.Tuft-DOX-CUR LPs), as compared to the single drug/peptide-loaded formulation (DOX LPs, CUR LPs, DOX-CUR LPs, P.Tuft- LPs, P.Tuft-DOX LPs, P.Tuft-CUR LPs). Western blot analysis revealed that the tumor inhibition was associated with p53-mediated apoptotic pathway. Further, the biochemical and histological analysis revealed that the various liposomal preparation used in this study were non-toxic to the animals at the specified dose (10mg/kg).Conclusion: In conclusion, we have developed a targeted liposomal formulation of P.Tuftsin-bearing liposomes co-encapsulated with effective anti-cancer drugs such as doxorubicin and curcumin. In experimental animals, tumor inhibition by P.Tuft-DOX-CUR LPs indicates the synergistic therapeutic effect of the peptide and the dual drug.Keywords: palmitoyl-tuftsin, antitumor, doxorubicin, curcumin
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- 2020
11. Human beta casein fragment (54-59) modulates M. bovis BCG survival and basic transcription factor 3 (BTF3) expression in THP-1 cell line
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Bhupendra N. Singh, Wahajul Haq, Raj Kamal Tripathi, Reshu Saxena, Vandana Singh, Seturam B. Katti, and Dharamsheela Thakur
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Bacterial Diseases ,Lipopolysaccharides ,Chemokine ,Proteome ,Applied Microbiology ,Gene Expression ,lcsh:Medicine ,Apoptosis ,Peptide ,Toxicology ,Biochemistry ,Intracellular Receptors ,Immunotoxicology ,Drug Discovery ,Molecular Cell Biology ,Gene expression ,Signaling in Cellular Processes ,Protein Isoforms ,THP1 cell line ,lcsh:Science ,Peptide sequence ,chemistry.chemical_classification ,Multidisciplinary ,Cell Death ,biology ,Caseins ,Nuclear Proteins ,Mycobacterium bovis ,Nuclear Signaling ,Infectious Diseases ,Host-Pathogen Interactions ,Medicine ,Cytokines ,Chemokines ,Research Article ,Biotechnology ,Signal Transduction ,Genetic Toxicology ,Immunology ,Molecular Sequence Data ,Down-Regulation ,Bioengineering ,Nitric Oxide ,Microbiology ,Cell Line ,Molecular Genetics ,Immune system ,Genetics ,Humans ,Immunologic Factors ,Amino Acid Sequence ,Biology ,Antibiotics, Antitubercular ,Transcription factor ,Microbial Viability ,lcsh:R ,Proteins ,Computational Biology ,Macrophage Activation ,Molecular biology ,Peptide Fragments ,chemistry ,Small Molecules ,Cell culture ,biology.protein ,lcsh:Q ,Transcription Factors - Abstract
Immunostimulatory peptides potentiate the immune system of the host and are being used as a viable adjunct to established therapeutic modalities in treatment of cancer and microbial infections. Several peptides derived from milk protein have been reported to induce immunostimulatory activity. Human β -casein fragment (54-59), natural sequence peptide (NS) carrying the Val-Glu-Pro-Ile-Pro-Tyr amino acid residues, was reported to activate the macrophages and impart potent immunostimulatory activity. In present study, we found that this peptide increases the clearance of M. bovis BCG from THP-1 cell line in vitro. The key biomolecules, involved in the clearance of BCG from macrophage like, nitric oxide, pro-inflammatory cytokines and chemokines, were not found to be significantly altered after peptide treatment in comparison to the untreated control. Using proteomic approach we found that BTF3a, an isoform of the Basic Transcription Factor, BTF3, was down regulated in THP-1 cell line after peptide treatment. This was reconfirmed by real time RT-PCR and western blotting. We report the BTF3a as a novel target of this hexapeptide. Based on the earlier findings and the results from the present studies, we suggest that the down regulation of BTF3a following the peptide treatment may augment the M. bovis BCG mediated apoptosis resulting in enhanced clearance of M. bovis BCG from THP-1 cell line.
- Published
- 2012
12. New acylides: synthesis of 3-O-[γ-(4-oxo-2-aryl-thiazolidin-3-yl)butyryl]erythromycin A derivatives
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Wahajul Haq, Seturam B. Katti, and Deepa Pandey
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Primary (chemistry) ,Stereochemistry ,Aryl ,Organic Chemistry ,Erythromycin ,Full Research Paper ,lcsh:QD241-441 ,chemistry.chemical_compound ,Chemistry ,lcsh:Organic chemistry ,chemistry ,medicine ,lcsh:Q ,Amine gas treating ,lcsh:Science ,medicine.drug - Abstract
Summary In search of new erythromycin derivatives 3-O-[γ-(4-oxo-2-aryl-thiazolidin-3-yl)butyryl]erythromycin A derivatives have been synthesized. The 3-hydroxy group was derivatised to a primary amine and subsequently the thiazolidinone nucleus was generated at the amino functionality through DCC mediated one-pot three-component reaction in good yields.
- Published
- 2008
13. An MVA vaccine overcomes tolerance to human p53 in mice and humans.
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Guang-Yun Song, Gibson, Glen, Wahajul Haq, Huang, Eric C. C., Srivasta, Tumul, Hollstein, Monica, Daftarian, Pirouz, Zhongde Wang, Diamond, Don, and Ellenhorn, Joshua D. I.
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VACCINES ,CANCER vaccines ,VIRUS diseases ,TUMORS ,PEPTIDES ,IMMUNE response ,DRUG therapy ,CYTOKINES - Abstract
The cellular regulatory protein p53 is overexpressed by almost 50% of all malignancies making it an attractive target for a vaccine approach to cancer. A number of immunotherapy approaches targeting p53 have been evaluated successfully in murine models, but translation of these preclinical findings to the clinic has been unsuccessful. Prior studies in our laboratory employing murine models demonstrated that a modified vaccinia virus Ankara (MVA) vaccine expressing murine p53 could stimulate p53 specific immunity. Systemic administration of the MVA vaccine was able to effect the rejection of established tumors. To better understand the immunologic mechanisms that underlie the vaccine function of human p53, we utilized a murine model in which the murine germ line copy of p53 was replaced with a modified human one. These mice, referred to as Hupki, were evaluated as a tolerant model to explore the capacity of MVA expressing human p53 to overcome tolerance and reject human p53-expressing tumors. MVAp53 immunization of Hupki mice resulted in the generation of p53-specific CD8
+ T cells and the rejection of a highly aggressive murine mammary carcinoma cell line 4T1(H-2d) transfected with human p53 (4T1p53). An immunologic correlate of tumor protection was evaluated utilizing an overlapping peptide library spanning the full length of human p53. This reagent was also used in combination with MVAp53 to stimulate p53-specific CD8+ T cell responses in cancer patients. These studies demonstrate the potential of MVAp53 to overcome tolerance to p53 for cancer immunotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2007
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14. Tryptophan residue is essential for immunoreactivity of a diagnostically relevant peptide epitope of A. fumigatus.
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Neel Kamal, Shantanu Chowdhury, Taruna Madan, Deepak Sharma, M. Attreyi, Wahajul Haq, Seturam Bandacharya Katti, Anil Kumar, and P. Usha Sarma
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Abstract The role of tryptophan (Trp17) in immunoreactivity of P1, the diagnostically relevant peptide from a major allergen/antigen of Aspergillus fumigatus, was evaluated by chemically modifying tryptophanyl residue of P1. In BIAcore kinetic studies, unmodified P1 showed a 100-fold higher binding with ABPA (Allergic Bronchopulmonary Aspergillosis) patients’ IgG [KD (equilibrium dissociation constant) = 2.74 e−8 ± 0.13 M] than the controls’ IgG (KD = 2.97 e−6± 0.14 M), whereas chemically-modified P1 showed similar binding [KD patients’ IgG = 3.25 e−7± 0.16 M, KD controls’ IgG = 3.86 e−7± 0.19 M] indicating loss of specific immunoreactivity of P1 on tryptophan modification. Modified P1 showed loss of specific binding to IgE and IgG antibodies of ABPA patients in ELISA (Enzyme-Linked Immunosorbent Assay). The study infers that tryptophan residue (Trp17) is essential for immunoreactivity of P1. [ABSTRACT FROM AUTHOR]
- Published
- 2005
15. Augmentation of human natural killer cells by splenopentin analogs
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Vijay K. Singh, K.B. Mathur, S. Biswas, Shyam S. Agarwal, Wahajul Haq, and A. Rastogi
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Lymphocyte ,Molecular Sequence Data ,Biophysics ,T-Cell Transformation ,Thymopoietins ,Pharmacology ,Splenopentin ,Lymphocyte Activation ,Biochemistry ,Pentapeptide repeat ,Natural killer cell ,Adjuvants, Immunologic ,Structural Biology ,NK. cell cytotoxicity ,Genetics ,medicine ,Humans ,Thymopoietin ,Amino Acid Sequence ,Molecular Biology ,Cells, Cultured ,Phytohaemagglutinin ,biology ,T-cell transformation ,Biological activity ,Cell Biology ,In vitro ,Peptide Fragments ,Killer Cells, Natural ,medicine.anatomical_structure ,Immunology ,biology.protein ,Immunomodulator - Abstract
Splenopentin, Arg-Lys-Glu-Val-Tyr (SP-5) and its synthetic analogs; Arg-d-Lys-Glu-Val-Tyr (pentapeptide 1), Lys-Lys-Glu-Val-Tyr (2), d-Lys-Lys-Glu-Val-Tyr (3), Arg-Lys-Gly-Val-Tyr (4), and Arg-Lys-Gln-Val-Tyr (5) have been examined for augmentation of human natural killer (NK) cell activity and human T-cell transformation response. Pentapeptides 2 and 3 were found to significantly augment the in vitro human NK cell activity. However, none of them had any effect on lymphocyte proliferative responses.
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