Conformational constraints: Nonpeptide β‐turn mimics

Abstract

The β‐turn, which has also been referred to as the β‐bend, β‐loop or reverse turn, has been implicated as an important site for molecular recognition in many biologically active peptides and in globular proteins. This small secondary structure therefore makes an attractive target for mimicry by a conformational constraint, because a peptide which is constrained in a biologically active conformation can display a number of advantages over the parent substrate. The less peptide‐like such a constraint is, the more potential there is to maximize these advantages. A decade has passed since the first (and highly successful) attempt to mimic the β‐turn with a nonpeptide conformational constraint was disclosed by Freidinger et al. (1980). Since this report, rapidly growing interest in the field of nonpeptide β‐turn mimics has seen a variety of experimental approaches and a mixed bag of results. It is attempted in this review, not only to summarize and critically analyse these approaches, but also to touch on the compexities associated with the conformational mimicry of such a diverse structure as the β‐turn.