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 Gly 1 -Asn 2 -Trp 3 -His 4 -Gly 5 -Thr 6 -Ala 7 -Pro 8 -Asp 9 -Trp 10 -Phe 11 -Phe 12 -Asn 13 - Tyr 14 -Tyr 15 - Trp 16 . The compound is cyclized between the β-carboxyl group of Asps and the α-amino group of Gly 1