BI-32169, a bicyclic 19-peptide with strong glucagon receptor antagonist activity from Streptomyces sp

J Nat Prod. 2004 Sep;67(9):1528-31. doi: 10.1021/np040093o.

Abstract

A new bicyclic 19-peptide, BI-32169, has been isolated from the culture broth of Streptomyces sp. (DSM 14996). Its structure has been established by amino acid analysis, mass spectrometry, and 2D NMR analysis. BI-32169 consists exclusively of protein amino acids and is cyclized from the side chain of Asp(9) to the N-terminus of Gly(1). One disulfide bond between Cys(6) and Cys(19) forms a bicyclic structure. BI-32169 and its methyl ester derivative showed potent inhibitory activity against the human glucagon receptor (IC(50) 440 and 320 nM, respectively) in a functional cell-based assay.

MeSH terms

  • Amino Acid Sequence
  • Humans
  • Inhibitory Concentration 50
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / isolation & purification*
  • Peptides, Cyclic / pharmacology
  • Receptors, Glucagon / antagonists & inhibitors*
  • Spain
  • Streptomyces / chemistry*

Substances

  • BI-32169
  • Peptides, Cyclic
  • Receptors, Glucagon