GE23077 A1/B1

Isolated from Actinomadura sp. White to off-white powder. Soluble in DMSO or water. Cyclic heptapeptide antibiotic. Potent and selective inhibitor of bacterial RNA polymerase (RNAP). Inhibits Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) RNAPs with IC50 ~20nM, whereas it is not active on E. coli DNA polymerase or on eukaryotic (wheat germ) RNAP II (IC50 values >100µM). Even though of its potent activity in vitro on purified bacterial RNAPs, it shows a narrow spectrum of antimicrobial activity in vivo on Gram-positive and Gram-negative bacteria, due to lack of memmbrane permeability. Acts at the level of transcription initiation. Binds directly to the bacterial RNA polymerase (RNAP) active-center 'i' and 'i+1' nucleotide binding sites, preventing the binding of initiating nucleotides and thereby preventing transcription initiation. Tool for mechanistic studies on bacterial RNAP and for potential anti-infective drug discovery.