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.
Fang
Xiao
X
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
Nam
Joonwoo
J
Shin
Dongwoo
D
Rew
Yosup
Y
Boger
Dale L
DL
Walker
Suzanne
S
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