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

I. CHARACTERIZATION OF PRODUCING STRAIN, FERMENTATION, ISOLATION, PHYSICO-CHEMICAL AND BIOLOGICAL PROPERTIES

Abstract

RES-701-1, a novel cyclic peptide endothelin antagonist, was isolated from the culture broth of Streptomyces sp. RE-701. RES-701-1 selectively inhibited the ET-1 binding to type B endothelin receptor (ET_B receptor) with an IC₅₀ of 10 nM expressed in CHO cells and blocked the ET-1-induced elevation of intracellular free Ca²⁺ concentration in ET_B receptor-expressing COS-7 cells. Characterization of producing strain, fermentation, isolation, structure, physico-chemical and biological properties of RES-701-1 are described.