Abstract

Proteins modulate the majority of all biological functions and are primarily composed of highly organized secondary structural elements such as helices, turns and sheets. Many of these functions are affected by a small number of key protein–protein contacts, often involving one or more of these well-defined structural elements. Given the ubiquitous nature of these protein recognition domains, their mimicry by peptidic and non-peptidic scaffolds has become a major focus of contemporary research. This review examines several key advances in secondary structure mimicry over the past several years, particularly focusing upon scaffolds that show not only promising projection of functional groups, but also a proven effect in biological systems.

Highlights

  • One of the fundamental tenets of biology is that protein structure dictates protein function

  • Just as protein structure dictates protein function, the ability of the synthetic molecule to mimic a given protein structure will directly affect its efficacy in a biological setting

  • This review examines several of the most important recent advances in this arena, focusing upon those that show the ability to mimic protein secondary structure, and to modulate protein function in a biological system

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Summary

Introduction

One of the fundamental tenets of biology is that protein structure dictates protein function. While some potency was lost, the best compound still exhibited 55 nM binding affinity, was cell permeable and importantly was able to restore apoptotic activity in compromised cells, unlike the wild-type peptide In another use of staple-based mimetics, the Fairlie group has developed an interesting, rationally designed, bi-cyclic peptide that is capable of adopting a highly α-helical structure in aqueous solution and disrupting RSV cell fusion (Shepherd et al 2006). This 13-mer is made of up two five-residue cyclic rings with three linear peripheral residues and is based upon a portion of the HR C -terminal (HR-C ) helix of the RSV F glycoprotein. These two properties suggest that the antenna system works as an effective system for artificial photosynthesis

Turn structures
H R3 O H
Coil-based structures
Findings
Conclusions
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