Antibiotic GE37468 A: A Novel Inhibitor of Bacterial Protein Synthesis. II. Structure Elucidation (original) (raw)

1995, The Journal of Antibiotics

GE2270 A, produced by Planobispora rosea ATCC53773, inhibits Gram-positive bacteria and anaerobes by acting on the bacterial protein synthesis. The structure has been determined by physico-chemical methods applied to the intact molecule and to the main hydrolysis products. Characterization by UV, IR, NMR(double quantum filter COSY), acid-base ionization, elemental analysis and FAB-MSindicated that GE2270 A is a highly modified peptide having MW1,289 and formula C56H55N15O10S6, and a weak basic function, and that it belongs to the thiazolyl peptide group of antibiotics. Acid hydrolysis yielded a main product (MW634), responsible for the chromophoric absorption, and a number of hydrolyzed products of lower MW. 13C NMRinverse techniques and MSstudies (El, positive ion chemical ionization, and collision induced dissociation FAB-MS-MSexperiments) on GE2270 A, the chromophoric compound, and the other hydrolysis products led to the complete identification of the various amino acid residues and their sequence. Two out of the six chiral centers have been determined. The structure is thought to originate from modification ofa chain of 14 amino acids in a process which creates 6 thiazole rings and one pyridine. The modification process also closes the linear polypeptide to form a cyclic part with an attached side-chain. GE2270 A plausibly has a similar biosynthetic origin to that of other thiazolyl peptide antibiotics such as nosiheptide and micrococcin. GE2270A is a new antibiotic isolated from the Planobispora rosea strain ATCC537731}. The mechanism of action of GE2270A is the specific inhibition of bacterial protein biosynthesis by acting on the elongation factor Tu (EF-Tu)1). GE2270 A was extracted with methanol from the mycelium and was purified by column chromatography on silica gel. After purification it is obtained as a white powder. GE2270 A is active in vitro against Gram-positive and a few Gram-negative bacteria. It is particularly active against anaerobes1*. Experimental The UVabsorption spectra were recorded with a Perkin-Elmer spectrophotometer model 320 in methanol solutions as such and at the extreme pH values obtained by adding a trace of HC1 or KOH. The IR absorption spectra were obtained from a mineral oil suspension and in chloroform solution with a Perkin-Elmer spectrophotometer model 580. The acid-base titrations in aqueous medium were obtained with 0.1 n KOHor with 0.1 N HC1on a

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