BI-32169, a bicyclic 19-peptide with strong glucagon receptor antagonist activity from Streptomyces sp.
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.
Potterat
Olivier
O
Boehringer Ingelheim Pharma GmbH and Co. KG, Birkendorfer Strasse 65, D-88397 Biberach an der Riss, Germany. olivier.potterat@bc.boehringer-ingelheim.com
Wagner
Klaus
K
Gemmecker
Gerd
G
Mack
Jürgen
J
Puder
Carsten
C
Vettermann
Regine
R
Streicher
Rüdiger
R
D000595:Amino Acid Sequence; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D013030:Spain; D013302:Streptomyces / Q000737:chemistry*
C493079:BI-32169; D010456:Peptides, Cyclic; D018027:Receptors, Glucagon