With the rising resistance of bacteria to currently employed chemotherapeutics there is a growing need for novel targets and paradigms to thwart this trend. �One compound, multiple targets� is a paradigm which aims to decrease the statistical likelihood the organism will develop mutations within the target genes necessary to confer clinically relevant resistance. UDP-N-acetylglucosamine acyltransferase (LpxA) and UDP-3-O-(R-3-hydroxymyristoyl)glucosamine acyltransferase (LpxD), the two essential acyltransferases in the lipid A biosynthetic pathway of Gram-negative bacteria, are inhibited by the dual binding peptide RJPXD33. To further examine this probe, a continuous, fluorescent acyltransferase assay was developed through exploitation of the lone thiol unveiled upon holo-Acyl carrier protein (ACP) following acyl group transfer. Holo-ACP reacts with the commercially available thiol-labeling reagent, ThioGlo1, generating a fluorescent conjugate which can be monitored at ?ex = 379 nm and ?em = 513 nm. Finally, the co-crystal structure of RJPXD33�acyltransferase is also presented.

Probing early acyltransferases of lipid A with inhibitory peptides

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.