Isolation and Purification of HS-142-1, a Novel Nonpeptide Antagonist for the Atrial Natriuretic Peptide Receptor, from Aureobasidium sp.

Abstract

During the screening program for atrial natriuretic peptide (ANP) receptor ligands of microbial origin, we isolated a novel nonpeptide ANP antagonist, HS-142-1, from a culture broth of Aureobasidium pullulans var. melanigenum. Structural analysis showed that HS-142-1 was composed of 20-30 kinds of β-1, 6-glucan esterified by caproyl groups; each component had an almost equal potency. HS-142-1 inhibited [¹²⁵I]-rANP binding to its receptor in rabbit kidney cortex membranes with an IC₅₀ of 0.3 μg/ml and antagonized ANP-induced cGMP production by bovine lung membranes in a dose-dependent fashion. The discovery of this nonpeptide ANP antagonist, HS-142-1, will provide a useful tool to study the physiological significance of natriuretic peptide system.