RES-701-1, a novel and selective endothelin type B receptor antagonist produced by Streptomyces sp. RE-701. II. Determination of the primary sequence

The structure of RES-701-1, a novel microbial endothelin type B receptor antagonist, was determined. Protein chemical data and FAB-MS have identified RES-701-1 to be a cyclic polypeptide consisting of 16 common L-amino acids. This compound is so stable against proteolysis that its enzymatic digestion under standard conditions proved to be very difficult. Therefore, the primary sequence of RES-701-1 was determined by the application of advanced protein chemical methods to be Gly1-Asn2-Trp3-His4-Gly5-Thr6-Ala7-Pro8-++ +Asp9-Trp10-Phe11-Phe12-Asn13- Tyr14-Tyr15-Trp16. The compound is cyclized between the beta-carboxyl group of Asp9 and the alpha-amino group of Gly1.