Bioactive and Model Peptides Characterized By the Helicogenic (alpha-me)phe Residue

We have synthesized and fully characterized the hypersweet super-aspartame analogue pCN-C6H4-NHCO-L-Asp-L-(alphaMe)Phe-OMe 1; the [D-(alphaMe)Phe]3-analogue of the formyl-methionyl tripeptide chemoattractant HCO-L-Met-L-Leu-D-(alphaMe)Phe-OMe 2, the first D-chemotactic peptide being found more active than its L-diastereomer; and the model pentapeptide pBrBz-D-(alphaMe)Phe-(Aib)2-D-(alphaMe)Phe-Aib-OtBu 3. The preferred conformation of the three peptides, as determined by X-ray diffraction analyses, is discussed in terms of the proposed receptor models for sweet perception [peptide 1] and neutrophil chemotaxis [peptide 4, and as a promising candidate for molecular recognition studies [peptide 3].