Peptidomimetics: A Synthetic Tool for Inhibiting Protein\u2013Protein Interactions in Cancer

Lloyd Mabonga,Abidemi Paul Kappo

doi:10.1007/s10989-019-09831-5

Lloyd Mabonga, Abidemi Paul Kappo

Open Access

https://doi.org/10.1007/s10989-019-09831-5

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Journal: Letters in Peptide Science	Publication Date: Feb 27, 2019
Citations: 56	License type: open-access

Affiliation: University of Zululand

Abstract

Protein–protein interactions (PPI) are vital in modulating biochemical pathways in many biological processes. Inhibiting PPI is a tremendously important diagnostic and therapeutic strategy in averting pathophysiological cues and disease progression. Targeting PPI as a smart drug discovery tool has been largely overlooked over the years due to their highly dynamic and expansive interfacial areas. However in recent years, researchers have developed new technologies that have the potential to move this approach up the technology development curve and enable the regular discovery of PPI-focused smart drugs. Few drugs are already on the market and some potential drug-like candidates are in clinical trials. In this study we review the application of peptidomimetics as a valuable tool in PPI inhibition in cancer. First, we describe PPI and the general properties of the PPI interface. Next, we discuss the classification of peptidomimetics. Lastly, we focus on the application of peptidomimetics on targeted PPI in cancer pathways.

Highlights

Protein–protein interactions (PPI) are well recognised mediators in biological processes and are vitally important in the progression of many disease states (Du et al 2018; Robertson and Spring 2018; Zhang et al 2018)
Due to the improving technology expertise, PPI have come to the spotlight as significant drug development targets
This review will focus on the application of synthetic mimicries to target PPI in cancer diagnostics and therapeutics

Summary

Introduction

Protein–protein interactions (PPI) are well recognised mediators in biological processes and are vitally important in the progression of many disease states (Du et al 2018; Robertson and Spring 2018; Zhang et al 2018). The disruption of PPI targeting hot spots regions using small molecule or peptide inhibitors both diagnostic and therapeutic significance (Robertson and Spring 2018). The generation of class A helix mimetics for MDM2 and MDMX using the peptide-stapling technique and thiol- and triazole-based cross-links observed a prominent increase of red, PDB 3V3B).

Results

Conclusion