Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase. II. Structure elucidation.
During the screening program for new antibacterial agents produced by actinomycetes, GE23077 was isolated from fermentation broths of an Actinomadura sp. strain as a complex of factors A1, A2, B1, B2. NMR, MS and GC/MS analysis carried out on the isolated components led to the conclusion that GE23077 is a novel cyclic heptapeptide consisting of common and unusual amino acids. The chemical structures of the complex components were elucidated. Components A and B differ in the structure of the acyl group connected to a 2,3-diaminopropanoic acid moiety. A alpha-amino-malonic acid residue in the peptidic sequence is the origin of an isomerization process between A1 and A2 as well as B1 and B2. The chirality of the alpha-amino-malonic acid residue can be inverted easily via keto-enol tautomerism. Factors A2 and B2 should be considered as epimers of A1 and B1 respectively. By degradation studies the absolute configuration of some amino acids were determined. Chiral GC-MS and Micellar Electrokinetic Capillary Chromatography (MEKC) were used to define the absolute stereochemistries of five out of ten chiral centers.
Marazzi
Alessandra
A
Vicuron Pharmaceuticals via R. Lepetit, 34, 21040, Gerenzano (Varese) Italy. amarazzi@vicuron.it
Kurz
Michael
M
Stefanelli
Stefania
S
Colombo
Luigi
L
D000596:Amino Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D020374:Chromatography, Micellar Electrokinetic Capillary; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D011492:Protein Hydrolysates; D021241:Spectrometry, Mass, Electrospray Ionization; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism
D000596:Amino Acids; D000900:Anti-Bacterial Agents; C489256:GE 23077-A; C489257:GE 23077-B; D010456:Peptides, Cyclic; D011492:Protein Hydrolysates; D012321:DNA-Directed RNA Polymerases