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8 results on '"Kumawat, Dhanraj"'

1. Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2

Author

Nguyen, Linh, McCord, Kelli A., Bui, Duong T., Bouwman, Kim M., Kitova, Elena N., Elaish, Mohamed, Kumawat, Dhanraj, Daskhan, Gour C., Tomris, Ilhan, Han, Ling, Chopra, Pradeep, Yang, Tzu-Jing, Willows, Steven D., Mason, Andrew L., Mahal, Lara K., Lowary, Todd L., West, Lori J., Hsu, Shang-Te Danny, Hobman, Tom, Tompkins, Stephen M., Boons, Geert-Jan, de Vries, Robert P., Macauley, Matthew S., and Klassen, John S.

Published
2022
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3. A Kinetic Trapping Approach for Facile Access to 3FaxNeu5Ac and a Photo-Cross-Linkable Sialyltransferase Probe

Author

Kumawat, Dhanraj, Gray, Taylor E., Garnier, Cole R., Bui, Duong T., Li, Zhixiong, Jame-Chenarboo, Zeinab, Jerasi, Jeremy, Wong, Warren O., Klassen, John S., Capicciotti, Chantelle J., and Macauley, Matthew S.

Abstract

Sialic acid (Neu5Ac) is installed onto glycoconjugates by sialyltransferases (STs) using cytidine monophosphate-Neu5Ac (CMP-β-d-Neu5Ac) as their donor. The only class of cell-active ST inhibitors are those based on a 3FaxNeu5Ac scaffold, which is metabolically converted into CMP-3FaxNeu5Ac within cells. It is essential for the fluorine to be axial, yet stereoselective installation of fluorine in this specific orientation is challenging. Sialic acid aldolase can convert 3-fluoropyruvate and 2-acetamido-2-deoxy-d-mannopyranose (ManNAc) to 3FNeu5Ac, but stereocontrol of the fluorine in the product has not been possible. We hypothesized that the 3Faxkinetic product of a sialic acid aldolase reaction could be trapped by coupling with CMP-sialic acid synthetase to yield CMP-3FaxNeu5Ac. Here, we report that highly active CMP-sialic acid synthetase and short reaction times produce exclusively CMP-3FaxNeu5Ac. Removal of CMP from CMP-3FaxNeu5Ac under acidic conditions unexpectedly led to 3-fluoro-β-d-Neu5Ac 2-phosphate (3FaxNeu5Ac-2P). Alkaline phosphatase successfully converted 3FaxNeu5Ac-2P to 3FaxNeu5Ac, enabling stereochemically controlled access to 3FaxNeu5Ac, which is effective in lowering the sialoglycan ligands for Siglecs on cells. Moreover, our kinetic trapping approach could be used to access CMP-3FaxNeu5Ac with modifications at the C5, C9, or both positions, which enabled the chemoenzymatic synthesis of a photo-cross-linkable version of CMP-3FaxNeu5Ac that selectively photo-cross-linked to ST6GAL1 over two other STs.

Published
2024
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4. Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2

Author

Nguyen, Linh, primary, McCord, Kelli A., additional, Bui, Duong T., additional, Bouwman, Kim M., additional, Kitova, Elena N., additional, Elaish, Mohamed, additional, Kumawat, Dhanraj, additional, Daskhan, Gour C., additional, Tomris, Ilhan, additional, Han, Ling, additional, Chopra, Pradeep, additional, Yang, Tzu-Jing, additional, Willows, Steven D., additional, Mason, Andrew L., additional, Mahal, Lara K., additional, Lowary, Todd L., additional, West, Lori J., additional, Hsu, Shang-Te Danny, additional, Hobman, Tom, additional, Tompkins, Stephen M., additional, Boons, Geert-Jan, additional, de Vries, Robert P., additional, Macauley, Matthew S., additional, and Klassen, John S., additional

Published
2021
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5. Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2

Author

Nguyen, Linh, McCord, Kelli A, Bui, Duong T, Bouwman, Kim M, Kitova, Elena N, Elaish, Mohamed, Kumawat, Dhanraj, Daskhan, Gour C, Tomris, Ilhan, Han, Ling, Chopra, Pradeep, Yang, Tzu-Jing, Willows, Steven D, Mason, Andrew L, Mahal, Lara K, Lowary, Todd L, West, Lori J, Hsu, Shang-Te Danny, Hobman, Tom, Tompkins, Stephen M, Boons, Geert-Jan, de Vries, Robert P, Macauley, Matthew S, Klassen, John S, Nguyen, Linh, McCord, Kelli A, Bui, Duong T, Bouwman, Kim M, Kitova, Elena N, Elaish, Mohamed, Kumawat, Dhanraj, Daskhan, Gour C, Tomris, Ilhan, Han, Ling, Chopra, Pradeep, Yang, Tzu-Jing, Willows, Steven D, Mason, Andrew L, Mahal, Lara K, Lowary, Todd L, West, Lori J, Hsu, Shang-Te Danny, Hobman, Tom, Tompkins, Stephen M, Boons, Geert-Jan, de Vries, Robert P, Macauley, Matthew S, and Klassen, John S

Published
2021

6. Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2

Author

Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Nguyen, Linh, McCord, Kelli A, Bui, Duong T, Bouwman, Kim M, Kitova, Elena N, Elaish, Mohamed, Kumawat, Dhanraj, Daskhan, Gour C, Tomris, Ilhan, Han, Ling, Chopra, Pradeep, Yang, Tzu-Jing, Willows, Steven D, Mason, Andrew L, Mahal, Lara K, Lowary, Todd L, West, Lori J, Hsu, Shang-Te Danny, Hobman, Tom, Tompkins, Stephen M, Boons, Geert-Jan, de Vries, Robert P, Macauley, Matthew S, Klassen, John S, Afd Chemical Biology and Drug Discovery, Sub Chemical Biology and Drug Discovery, Chemical Biology and Drug Discovery, Nguyen, Linh, McCord, Kelli A, Bui, Duong T, Bouwman, Kim M, Kitova, Elena N, Elaish, Mohamed, Kumawat, Dhanraj, Daskhan, Gour C, Tomris, Ilhan, Han, Ling, Chopra, Pradeep, Yang, Tzu-Jing, Willows, Steven D, Mason, Andrew L, Mahal, Lara K, Lowary, Todd L, West, Lori J, Hsu, Shang-Te Danny, Hobman, Tom, Tompkins, Stephen M, Boons, Geert-Jan, de Vries, Robert P, Macauley, Matthew S, and Klassen, John S

Published
2021

7. Sialic acid-Dependent Binding and Viral Entry of SARS-CoV-2

Author

Nguyen, Linh, primary, McCord, Kelli, additional, Bui, Duong, additional, Bouwman, Kim, additional, Kitova, Elena, additional, Kumawat, Dhanraj, additional, Daskhan, Gour, additional, Tomris, Ilhan, additional, Han, Ling, additional, Chopra, Pradeep, additional, Yang, Tzu-Jing, additional, Willows, Steven, additional, Lowary, Todd, additional, West, Lori, additional, Hsu, Shang-Te Danny, additional, Tompkins, Stephen, additional, Boons, Geert-Jan, additional, Mason, Andrew, additional, de Vries, Robert, additional, Macauley, Matthew, additional, and Klassen, John, additional

Published
2021
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8. A Kinetic Trapping Approach for Facile Access to 3F ax Neu5Ac and a Photo-Cross-Linkable Sialyltransferase Probe.

Author

Kumawat D, Gray TE, Garnier CR, Bui DT, Li Z, Jame-Chenarboo Z, Jerasi J, Wong WO, Klassen JS, Capicciotti CJ, and Macauley MS

Subjects
Kinetics, Humans, N-Acetylneuraminic Acid chemistry, N-Acetylneuraminic Acid metabolism, Photochemical Processes, Molecular Structure, Molecular Probes chemistry, Sialyltransferases metabolism
Abstract

Sialic acid (Neu5Ac) is installed onto glycoconjugates by sialyltransferases (STs) using cytidine monophosphate-Neu5Ac (CMP-β-d-Neu5Ac) as their donor. The only class of cell-active ST inhibitors are those based on a 3F ax Neu5Ac scaffold, which is metabolically converted into CMP-3F ax Neu5Ac within cells. It is essential for the fluorine to be axial, yet stereoselective installation of fluorine in this specific orientation is challenging. Sialic acid aldolase can convert 3-fluoropyruvate and 2-acetamido-2-deoxy-d-mannopyranose (ManNAc) to 3FNeu5Ac, but stereocontrol of the fluorine in the product has not been possible. We hypothesized that the 3F ax kinetic product of a sialic acid aldolase reaction could be trapped by coupling with CMP-sialic acid synthetase to yield CMP-3F ax Neu5Ac. Here, we report that highly active CMP-sialic acid synthetase and short reaction times produce exclusively CMP-3F ax Neu5Ac. Removal of CMP from CMP-3F ax Neu5Ac under acidic conditions unexpectedly led to 3-fluoro-β-d-Neu5Ac 2-phosphate (3F ax Neu5Ac-2P). Alkaline phosphatase successfully converted 3F ax Neu5Ac-2P to 3F ax Neu5Ac, enabling stereochemically controlled access to 3F ax Neu5Ac, which is effective in lowering the sialoglycan ligands for Siglecs on cells. Moreover, our kinetic trapping approach could be used to access CMP-3F ax Neu5Ac with modifications at the C5, C9, or both positions, which enabled the chemoenzymatic synthesis of a photo-cross-linkable version of CMP-3F ax Neu5Ac that selectively photo-cross-linked to ST6GAL1 over two other STs.

Published
2024
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