Assessing and utilizing esterase specificity in antimicrobial prodrug development.
Journal:
Methods in enzymology
PMID:
35331374
Abstract
As a class of enzymes, esterases have been investigated for decades and have found use in industrial processes, synthetic organic chemistry, and elsewhere. Esters are functional groups composed of an alcohol moiety and a carboxylic acid moiety. Although much work has explored the influence of the carboxyl moiety of an ester on its susceptibility to esterases, little work has explored the influence of the alcohol moiety. Here, we describe an in vitro methodology to explore the influence of changing the alcohol moiety of an ester on its enzymatic hydrolysis, including strategies for analyzing such data. We then describe leveraging data from these assays to develop targeted antimicrobial prodrugs that activate in certain species due to the discriminatory activity of species-specific esterases. We envisage the potential of genomics and machine learning to further these efforts. Finally, we anticipate the potential future uses of these ideas, including developing targeted anti-cancer compounds.