Antibiotics A21459 A and B, New Inhibitors of Bacterial Protein Synthesis. II. Structure Elucidation (original) (raw)
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Antibiotic GE37468 A: A Novel Inhibitor of Bacterial Protein Synthesis. II. Structure Elucidation
The Journal of Antibiotics, 1995
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
The Journal of Antibiotics, 1991
Newly synthesized 5-acylaminothiazolium salts and one 5-acylaminothiazolidine, considering their chemical structure and reactivity, have been proposed as potential inhibitors of bacterial serine DD-peptidases. A moderate antibiotic activity with (5-phenylacetylamino-3-thiazolio)acetate and (5-phenylacetylaminothiazolidin-3-yl)acetic acid was observed on Staphylococcus aureus ATCC 25923. The methyl-and tert-b\xty\ esters of the thiazolium salt have shown lower MIC values. Moreover, when introduced into an exponential growth phase culture of S. aureus, the three active thiazolium salts induced a partial lysis indicating an impairing of the bacterial cell wall biosynthesis. The observed time-dependent binding of the best compoundto the PBPs of S. aureus was too slow and occurred at too high concentrations to account for its MIC value. Consequently, the antibiotic activity of the thiazolium salts on the S. aureus cells seems not to be satisfactorily explained by a penicillin-like interaction with the PBPs.
A Chemist's Survey of Different Antibiotic Classes
Targets, Mechanisms and Resistance, 2013
Aminoglycosides (Figure 1.1) were first established as antibiotics in the 1940s and are still widely used worldwide. They are obtained by fermentation of Streptomyces, Micromonospora, and Bacillus; irreversibly inhibit protein synthesis by acting on the ribosome; and are especially active against gram-negative bacteria. They chemically consist of an aminocyclitol substituted with amino sugars. A classification proposed by Umezawa was based on the central structure, which can be streptamine 1, 2-deoxystreptamine 2, or streptidine 3. A relevant number of natural and semisynthetic derivatives have been obtained since their discovery with the aim of bettering the toxicity issues linked to these structures, mainly oto-and nephrotoxicity, and to fight the increased resistance that mostly arises from structural modification of the
LL-AF283 antibiotics, cyclic biphenyl peptides
The Journal of Antibiotics
The isolation of water soluble, basic antibiotics LL-AF283a and /? from the fermentation of Streptomycesfilipinensis was previously reported 1 '2). The antibiotic complex contained four components,
In vitro antimicrobial activity of a new antibiotic, MDL 62,879 (GE2270 A)
Antimicrobial Agents and Chemotherapy, 1993
MDL 62,879 (GE2270 A) is a new peptide antibiotic that inhibits protein synthesis through an interaction with elongation factor Tu. MDL 62,879 was very active against gram-positive clinical isolates, particulariy staphylococci and enterococci, for which MICs for 90% of isolates were <0.13 pg/ml. It was equally active against isolates resistant to ji-lactams, erythromycin, gentamicin, and glycopeptides. It also had activity against Mycobacterium tuberculosis. MDL 62,879 had moderate bactericidal activity against staphylococci.