Cochinmicins, novel and potent cyclodepsipeptide endothelin antagonists from a Microbispora sp. II. Structure determination

J Antibiot (Tokyo). 1992 Nov;45(11):1717-22. doi: 10.7164/antibiotics.45.1717.

Abstract

Cochinmicins I, II, and III are competitive endothelin antagonists produced by Microbispora sp. ATCC 55140. The cochinmicins are cyclic depsipeptides containing six alpha-amino acids and a pyrrolecarboxylic acid. Based upon MS, 1D and 2D NMR, and LC data, the structures and absolute stereochemistries of the cochinmicins have been assigned. All three components have the same basic sequence and contain one equivalent each of D-allo-threonine, D-alanine, L-phenylalanine, D-phenylalanine, 5-chloropyrrole-2-carboxylic acid (or pyrrole-2-carboxylic acid in cochinmicin I), plus two equivalents of 3,5-dihydroxyphenylglycine (DHPG). The phenylalanine residues were differentiated via a methanolysis product which contained only one of the phenylalanine residues. Both DHPG residues have the D configuration in the more active cochinmicins I and III. Cochinmicin II contains both D- and L-DHPG and these residues have been differentiated in the sequence based upon 1H NMR data.

MeSH terms

  • Amino Acid Sequence
  • Endothelins / antagonists & inhibitors*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Micromonosporaceae / metabolism*
  • Molecular Conformation
  • Molecular Sequence Data
  • Molecular Structure
  • Molecular Weight
  • Peptides, Cyclic / chemistry*
  • Spectrometry, Mass, Fast Atom Bombardment

Substances

  • Endothelins
  • Peptides, Cyclic
  • cochinmicin I
  • cochinmicin II
  • cochinmicin III