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

A new bicyclic 19-peptide, BI-32169 (1), 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 (2) showed potent inhibitory activity against the human glucagon receptor (IC50 440 and 320 nM, respectively) in a functional cell-based assay.