Helix construction using α-aminoisobutyryl residues in a modular approach to synthetic protein design. Conformational properties of an apolar decapeptide in two different crystal forms and in solution

Abstract

A modular strategy for the assembly of synthetic protein mimics is outlined. This approach is based on the ability of α -aminoisobutyric acid (Aib) to promote helical folding in peptides. The design of apolar, peptide helices with a high solubility in organic solvents facilitates structural design based on stereochemical constraints imposed by chosen non-protein residues. The design of individual helices is illustrated by the analysis of the decapeptide Boc-Aib-Ala-Leu-A!a-Aib-Aib-Leu-~Ala-Leu-Aib-OMe. Crystal structures of two polymorphic forms reveal an almost completely α-helical backbone. These high-resolution structures permit detailed characterization of the helix. H NMR and CD studies demonstrate maintenance of the helical conformation in solution, a feature that is a consequence of the limited flexibility of Aib residues in φ, ψ space.