Aib residues in peptaibiotics and synthetic sequences: Analysis of nonhelical conformations

Abstract

The α-aminoisobutyric (Aib) residue has generally been considered to be a strongly helicogenic residue as evidenced by its ability to promote helical folding in synthetic and natural sequences. Crystal structures of several peptide natural products, peptaibols, have revealed predominantly helical conformations, despite the presence of multiple helix-breaking Pro or Hyp residues. Survey of synthetic Aib-containing peptides shows a preponderance of 3₁₀-α, α-, and mixed 310/α-helical structures. This review highlights the examples of Aib residues observed in nonhelical conformations, which fall primarily into the polyproline II (P_II) and fully extended regions of conformational space. The achiral Aib residue can adopt both left (α_L)- and right (α_R)-handed helical conformations. In sequences containing chiral amino acids, helix termination can occur by means of chiral reversal at an Aib residue, resulting in formation of a Schellman motif. Examples of Aib residues in unusual conformations are illustrated by surveying a database of Aib-containing crystal structures.