Isolation and Structural Elucidation of Cyclic Tetrapeptides From Onychocola Sclerotica

J Nat Prod. 2012 Jun 22;75(6):1210-4. doi: 10.1021/np3000987. Epub 2012 Jun 13.

Abstract

Three new cyclic tetrapeptides (1-3) have been isolated from the crude fermentation extract of Onychocola sclerotica. The planar structures of 1-3 were elucidated by detailed spectroscopic analyses using one- and two-dimensional NMR experiments and high-resolution mass spectrometry. The absolute configuration of the amino acid residues in each cyclotetrapeptide was established by Marfey's method. Compounds 1-3 displayed activity as cardiac calcium channel blockers (Cav1.2) but did not inhibit the hERG potassium channel and were not cytotoxic. These peptides are the first secondary metabolites ever reported from fungi of the order Arachnomycetales.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids
  • Ascomycota / chemistry*
  • Calcium Channels, L-Type / drug effects
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / drug effects
  • Fermentation
  • Humans
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification*
  • Peptides, Cyclic / pharmacology
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / isolation & purification*
  • Vasodilator Agents / pharmacology

Substances

  • Amino Acids
  • Calcium Channels, L-Type
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • L-type calcium channel alpha(1C)
  • Peptides, Cyclic
  • Vasodilator Agents
  • cyclo-(N-MePhe-Ile)2
  • cyclo-(N-MePhe-Val)2
  • cyclo-(N-MePhe-Val-N-MePhe-Ile)