Potent antagonistic action of synthetic analogues of APGWGNamide, an antagonist of molluscan neuropeptide APGWamide

Abstract

Fifty-five kinds of analogues of APGWGNamide (Ala–Pro–Gly–Trp–Gly–Asn–NH 2), which is an antagonist of molluscan neuropeptide APGWamide, were synthesized and their antagonistic activities were examined on two molluscan smooth muscles. Among all the analogues tested, on spontaneous contraction of the crop of the land snail, Euhadra congenita, APGWG( l-biphenylalanine, Bip)amide showed the most potent antagonistic activity and its potency was 50–100 times higher than that of APGWGNamide. Likewise, on phasic contraction of the anterior byssus retractor muscle (ABRM) of the sea mussel, Mytilus edulis, the effect of APGWG( d-homophenylalanine, dHfe) was the most potent and showed 5–10 times stronger activity than that of APGWGNamide . In the tolerance test to known exo- and endopeptidases or the crop tissue homogenate, APGWGNamide was not only easily degraded by a proline-specific endopeptidase but also by the homogenate. Two kinds of potent antagonists were thus developed: APGWG(Bip)amide and APGWG(dHfe)amide, which will be useful tools for investigation of the function of APGWamide in the snail and the mussel, respectively.