RES-701-1, A NOVEL AND SELECTIVE ENDOTHELIN TYPE B RECEPTOR ANTAGONIST PRODUCED BY Streptomyces sp. RE-701

II. DETERMINATION OF THE PRIMARY SEQUENCE

Abstract

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-Asp^9-Trp¹⁰-Phe¹¹-Phe¹²- Asn¹³-Tyr¹⁴-Tyr¹⁵-Trp¹⁶. The compound is cyclized between the β-carboxyl group of Asp⁹ and the α-amino group of Gly¹.