Title: Mimetics of the Peptide β-Strand
Volume: 2
Issue: 5
Author(s): Matthew P. Glenn and David P. Fairlie
Affiliation:
Keywords:
peptide, drug-like properties, conformationally biased, peptidomimetics
Abstract: Bioactive structures of peptides represent important clues for drug discovery and development although peptides themselves have substantial limitations as drugs. One promising approach to overcoming the limitations of peptides is to progressively replace amide bonds in peptides with non-peptidic constraints that bring drug-like properties like stability and bioavailability to the molecules. These constraints can also be used to mould molecules into shapes which mimic key elements of protein secondary structure that confer bioactivity to protein surfaces. Preorganizing a molecule into the shape recognized by a receptor results in high affinity binding though a considerable entropy saving and is an effective approach to engineering highly bioactive drug leads. One peptide structure, the extended beta strand, has only recently been identified as a fundamental recognition element in physiological processes. Relatively few molecules have been described as constrained mimics of extended peptide conformations. We now summarize some approaches to mimicking peptide beta strands, and illustrate these with examples of bioactive, stable and bioavailable molecules that are conformationally biased to mimic the extended peptide beta strand.
