Linear α-human atrial natriuretic peptide analogs display receptor binding activity and inhibit α-hANP-induced cGMP accumulation

We have synthesized a series of [Cys(R) 7,23]α-hANP analogs, in which the two Cys residues were modified with various alkyl groups(R); i.e., R=Acm, Pe, Qe, Cam, Me, Ae, Bzl, Cm, Ocam and sulfo. The Acm-, Cam-, and Me-analogs exhibited binding activity as potent as α-hANP in rat vascular smooth muscle cells (VSMC). Binding activity of the analogs decreased progressively as the bulkiness of the R group increased. None of the analogs caused accumulation of cGMP in VSMC and vasorelaxant activity in rat aorta. Acm-, Cam- and Me-analogs substantially antagonized α-hANP-induced cGMP accumulation, but did not antagonize vasorelaxation induced by α-hANP in vitro.