Synthesis and activity profiles of atrial natriuretic peptide (ANP) analogs with reduced ring size

Abstract

Three deletion analogs of the atrial natriuretic peptide, [desGly-120]-ANP(103-126), [desLeu119, desGly120]ANP(103-126) and [desGly118,120,-desLeu119]-ANP(103-126), were synthesized by the solid-phase method. Successive elimination of the non-functional residues in positions 120-118 of the peptide sequence resulted in a progressive potency reduction in the rabbit aorta assay, in the bioassay monitoring suppression of aldosterone secretion from bovine zona glomerulosa cells and in a binding assay based on displacement of radioiodinated ANP(101-126) from bovine zona glomerulosa cell membranes. The fact that the deletion analogs showed quantitatively different relative potencies in each of the three in vitro assay systems was interpreted as further evidence in support of the existence of two or more classes of ANP receptors or binding sites.