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Your search keyword '"Guetschow, Erik D."' showing total 18 results
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18 results on '"Guetschow, Erik D."'

1. Orally Bioavailable Macrocyclic Peptide That Inhibits Binding of PCSK9 to the Low Density Lipoprotein Receptor

Author

Johns, Douglas G., Campeau, Louis-Charles, Banka, Puja, Bautmans, An, Bueters, Tjerk, Bianchi, Elisabetta, Branca, Danila, Bulger, Paul G., Crevecoeur, Inne, Ding, Fa-Xiang, Garbaccio, Robert M., Guetschow, Erik D., Guo, Yan, Ha, Sookhee N., Johnston, Jennifer M., Josien, Hubert, Kauh, Eunkyung A., Koeplinger, Kenneth A., Kuethe, Jeffrey T., Lai, Eseng, Lanning, Christine L., Lee, Anita Y.H., Li, Li, Nair, Anilkumar G., O’Neill, Edward A., Stoch, S. Aubrey, Thaisrivongs, David A., Tucker, Thomas J., Vachal, Petr, van Dyck, Kristien, Vanhoutte, Frederic P., Volckaert, Bram, Wolford, Dennis G., Xu, Andy, Zhao, Tian, Zhou, Dan, Zhou, Susan, Zhu, Xiaohong, Zokian, Hratch J., Walji, Abbas M., and Wood, Harold B.

Published
2023
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2. Development of a Green and Sustainable Manufacturing Process for a Key Intermediate to Nemtabrutinib (MK-1026): Sequential Deprotonation–Lithiation as a Batch–Flow Process

Author

Otte, Douglas A. L., primary, Larson, Reed T., additional, Alwedi, Embarek, additional, Armiger, Travis, additional, Chen, Yonggang, additional, Chung, Cheol K., additional, Corry, James, additional, Desmond, Richard, additional, Fier, Patrick S., additional, Franklin, Robert D., additional, Guetschow, Erik D., additional, Hall, Jackson R., additional, Halsey, Holst M., additional, Hartmanshenn, Clara, additional, Jellett, Lisa, additional, Kuhl, Nadine, additional, Lévesque, François, additional, McMullen, Jonathan P., additional, Patel, Pratiq A., additional, Paulines, Mellie June, additional, Ren, Hong, additional, Rodrigues, Vailankanni L., additional, Ruccolo, Serge, additional, Tan, Lushi, additional, Thaisrivongs, David A., additional, and Xiao, Kai-Jiong, additional

Published
2024
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3. Pilot-Scale Operation and Characterization of an Organolithium-Mediated Coupling Reaction in Flow to Form a Ketone Intermediate on the Route to Nemtabrutinib

Author

Franklin, Robert D., primary, Armiger, Travis, additional, Otte, Douglas A. L., additional, Larson, Reed T., additional, Spencer, Glenn, additional, Patel, Pratiq A., additional, Paulines, Mellie June, additional, Hall, Jackson R., additional, Xiao, Kai-Jiong, additional, Fier, Patrick S., additional, Rodrigues, Vailankanni L., additional, Guetschow, Erik D., additional, Kuhl, Nadine, additional, Jellett, Lisa, additional, Corry, James, additional, Chung, Cheol K., additional, and Thaisrivongs, David A., additional

Published
2024
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5. Manufacturing Process Development for the Biaryl Ether Fragment of Nemtabrutinib (MK-1026)

Author

Deprez, Nicholas R., primary, Rose, Harrison B., additional, Peters, Byron K., additional, Diaz-Santana, Anthony, additional, Liu, Zhuqing, additional, Kuhl, Nadine, additional, Chung, Cheol K., additional, Liu, Zhu, additional, Newman, Justin A., additional, Corry, James, additional, Guetschow, Erik D., additional, Hoyt, Erik, additional, Jellett, Lisa, additional, Kapil, Sunayana, additional, Poirier, Marc, additional, Shevlin, Michael, additional, Sirota, Eric, additional, Solovyov, Andrew, additional, Sun, Alexandra C., additional, and Thaisrivongs, David A., additional

Published
2023
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6. pH-Switchable Phase-Transfer Agents for Host Cell Protein Rejection in the Cascaded Biocatalytic Synthesis of an Active Pharmaceutical Ingredient

Author

Winston, Matthew S., primary, Poirier, Marc, additional, Liu, Zhijian, additional, Peng, Feng, additional, Humphrey, Guy R., additional, McIntosh, John A., additional, Reibarkh, Mikhail, additional, Wang, Fengqiang, additional, Guetschow, Erik D., additional, Castro, Steve, additional, Hoyt, Erik, additional, Lamberto, David J., additional, and Sirk, Kevin, additional

Published
2022
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10. Mass Activated Droplet Sorting (MADS) Enables High‐Throughput Screening of Enzymatic Reactions at Nanoliter Scale

Author

Holland‐Moritz, Daniel A., primary, Wismer, Michael K., additional, Mann, Benjamin F., additional, Farasat, Iman, additional, Devine, Paul, additional, Guetschow, Erik D., additional, Mangion, Ian, additional, Welch, Christopher J., additional, Moore, Jeffrey C., additional, Sun, Shuwen, additional, and Kennedy, Robert T., additional

Published
2020
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17. Droplet Microfluidics Coupled to Microchip Electrophoresis for High-Throughput Enzyme Modulator Screening.

Author

Guetschow, Erik D.

Subjects
Microfluidics, Electrophoresis, segmented flow, High-throughput screening
Abstract

High-throughput screening (HTS) represents a powerful tool for drug discovery by allowing tens of thousands of assays to be completed within a single day. Typically, assays are performed in multiwell plates (MWPs) utilizing fluorogenic substrates for detection. These substrates increase development time and can introduce artifactual results. Therefore, alternate screening strategies based around natural substrates are necessary. We developed a screening platform that couples nanoliter volume samples to microchip electrophoresis for analysis using a novel polydimethylsiloxane (PDMS)-and-glass microfluidic device. The system was demonstrated by screening a small library against protein kinase A (PKA), which regulates metabolism within the cell. It was chosen for its well-characterized kinetic parameters and commercially available peptide substrates. Sample throughput of 0.16 Hz was achieved allowing at least 6 replicate MCE injections from each sample in a high quality assay (Z’-factor = 0.8). To demonstrate the ability to screen larger libraries, we developed a novel assay for sirtuin 5 (SIRT5) using a naturally derived peptide substrate. SIRT5 impacts metabolism and has reported oncogenic functions making inhibitor identification of clinical importance. Compared to the PKA assay previously developed, assay throughput was increased 3-fold and 1406 samples were analyzed within 46 minutes (0.5 Hz). Using a 250 ms separation, each assay sample could be analyzed 8 times by MCE generating over 11,000 electropherograms. Several previously unreported inhibitors of SIRT5 were identified and verified by dose-response analysis. Finally, work toward miniaturization of high-throughput assays was demonstrated by performing sample preparation and analysis completely within nanoliter volume droplets. A simple to use and easy to fabricate PDMS microfluidic device was developed to allow addition of assay reagents to nanoliter volume samples. Reagent use, relative to assays performed in 384 well plates, could be reduced 1,000-fold and sample-to-sample carryover was less than 5 percent under typical experimental conditions. Analysis of samples prepared in droplet format was demonstrated with droplets containing a fluorescent dye and addition of a fluorescent peptide. These samples could be analyzed by MCE at 0.33 samples per second but increased throughput should be possible by using higher flow rates.

Published
2016

18. Mass Activated Droplet Sorting (MADS) Enables High-Throughput Screening of Enzymatic Reactions at Nanoliter Scale.

Author

Holland-Moritz DA, Wismer MK, Mann BF, Farasat I, Devine P, Guetschow ED, Mangion I, Welch CJ, Moore JC, Sun S, and Kennedy RT

Subjects
Algorithms, Enzyme Activation, Feasibility Studies, Imidazoles chemistry, Microfluidic Analytical Techniques, Pyridines chemistry, Spectrometry, Mass, Electrospray Ionization, Amines analysis, Enzyme Assays methods, High-Throughput Screening Assays methods, Microfluidics methods, Pyridines analysis, Transaminases metabolism
Abstract

Microfluidic droplet sorting enables the high-throughput screening and selection of water-in-oil microreactors at speeds and volumes unparalleled by traditional well-plate approaches. Most such systems sort using fluorescent reporters on modified substrates or reactions that are rarely industrially relevant. We describe a microfluidic system for high-throughput sorting of nanoliter droplets based on direct detection using electrospray ionization mass spectrometry (ESI-MS). Droplets are split, one portion is analyzed by ESI-MS, and the second portion is sorted based on the MS result. Throughput of 0.7 samples s -1 is achieved with 98 % accuracy using a self-correcting and adaptive sorting algorithm. We use the system to screen ≈15 000 samples in 6 h and demonstrate its utility by sorting 25 nL droplets containing transaminase expressed in vitro. Label-free ESI-MS droplet screening expands the toolbox for droplet detection and recovery, improving the applicability of droplet sorting to protein engineering, drug discovery, and diagnostic workflows., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2020
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