Biological properties of two models of calcitonin gene related peptide with idealized amphiphilic .alpha.-helices of different lengths

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Abstract
Previous studies on calcitonin gene related peptide (CGRP) have demonstrated that it has the characteristics of an amphiphilic peptide, and from an examination of the sequence, we have proposed that it contains as amphiphilic .alpha.-helix. We have synthesized two analogues of CGRP which have different lengths of idealized amphiphilic .alpha.-helical secondary structure. The first model, CGRM-1, has been substituted with residues generating an idealized amphiphilic .alpha.-helix in the region between residues 8 and 25, equivalent to approximately five turns of an .alpha.-helix. This peptide is not an agonist in any of our bioassays, but it does bind with low affinity to rCGRP receptors in crude liver membranes. Our second model, CGRM-2, has an idealized amphiphilic .alpha.-helix between residues 8 and 18, which is equivalent to approximately three turns of an .alpha.-helix. In an in vitro rat vas deferens assay, this peptide is an agonist with a potency one-fourth that of the native hormone. However, the potency of CGRM-2 in an adenylate cyclase assay is much lower, only 1/140th the potency of CGRP. Both model peptides display amphiphilic characteristics commensurate with their design. We conclude that there is an amphiphilic .alpha.-helix in rCGRP between residues 8 and 18 and that this helix terminates in the vicinity of residue 18.