Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10594510 | Bioorganic & Medicinal Chemistry Letters | 2012 | 5 Pages |
Abstract
This report provides a synopsis of the esterase processing of short chain fatty acid (SCFA)-derivatized hexosamine analogs used in metabolic glycoengineering by demonstrating that the extracellular hydrolysis of these compounds is comparatively slow (e.g., with a t1/2 of â¼4Â h to several days) in normal cell culture as well as in high serum concentrations intended to mimic in vivo conditions. Structure-activity relationship (SAR) analysis of common sugar analogs revealed that O-acetylated and N-azido ManNAc derivatives were more refractory against extracellular inactivation by FBS than their butanoylated counterparts consistent with in silico docking simulations of Ac4ManNAc and Bu4ManNAc to human carboxylesterase 1 (hCE1). By contrast, all analogs tested supported increased intracellular sialic acid production within 2Â h establishing that esterase processing once the analogs are taken up by cells is not rate limiting.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Mohit P. Mathew, Elaine Tan, Shivam Shah, Rahul Bhattacharya, M. Adam Meledeo, Jun Huang, Freddy A. Espinoza, Kevin J. Yarema,