Functional and biochemical analysis of a key series of ramoplanin analogues.
Ramoplanin is a potent lipoglycodepsipeptide antibiotic that is active against a wide range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE). It acts as an inhibitor of peptidoglycan (PG) biosynthesis that disrupts glycan chain polymerization by binding and sequestering Lipid II, a PG precursor. Herein, we report the functional antimicrobial activity (MIC, S. aureus) and fundamental biochemical assessments against a peptidoglycan glycosyltransferase (Escherichia coli PBP1b) of a set of key alanine scan analogues of ramoplanin that provide insight into the importance and role of each of its individual amino acid residues.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Xiao
X
Fang
Joonwoo
J
Nam
Dongwoo
D
Shin
Yosup
Y
Rew
Dale L
DL
Boger
Suzanne
S
Walker
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D047630:Depsipeptides / Q000737:chemistry* / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology; D006094:Gram-Positive Bacteria / Q000187:drug effects; D046928:Peptidoglycan Glycosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000900:Anti-Bacterial Agents; D047630:Depsipeptides; C041438:ramoplanin; D046928:Peptidoglycan Glycosyltransferase