Interfering peptides targeting protein-protein interactions: the next generation of drugs?

被引：106

作者：

Bruzzoni-Giovanelli, Heriberto ^{[1
,2
,3
]}

Alezra, Valerie ^{[4
]}

Wolff, Nicolas ^{[5
]}

Dong, Chang-Zhi ^{[1
,6
]}

Tuffery, Pierre ^{[1
,7
]}

Rebollo, Angelita ^{[8
]}

机构：

[1] Univ Sorbonne Paris Cite, Univ Paris 7 Denis Diderot, Paris, France

[2] INSERM, UMRS 1160, Paris, France

[3] Hop St Louis, AP HP, INSERM, Ctr Invest Clin 1427, Paris, France

[4] Univ Paris Saclay, Univ Paris Sud, CNRS,Fac Sci Orsay, Lab Methodol Synth & Mol Therape,ICMMO,UMR 8182, Paris, France

[5] CNRS, Inst Pasteur, Unite Resonance Magnet Nucl Biomol, UMR 3528, F-75015 Paris, France

[6] CNRS, ITODYS, UMR 7086, Paris, France

[7] INSERM, UMR S 973, RPBS, Paris, France

[8] UPMC, INSERM, Hop Pitie Salpetriere, CIMI Paris,U1135, Paris, France

来源：

DRUG DISCOVERY TODAY | 2018年 / 23卷 / 02期

关键词：

CELL-PENETRATING PEPTIDES; STRUCTURE-BASED DESIGN; IN-VIVO; STAPLED PEPTIDES; CYCLIC-PEPTIDES; BINDING-SITES; CONSTRAINED PEPTIDES; MACROCYCLIC PEPTIDES; STRUCTURE PREDICTION; CELLULOSE MEMBRANES;

D O I：

10.1016/j.drudis.2017.10.016

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Protein-protein interactions (PPIs) are well recognized as promising therapeutic targets. Consequently, interfering peptides (IPs) - natural or synthetic peptides capable of interfering with PPIs - are receiving increasing attention. Given their physicochemical characteristics, IPs seem better suited than small molecules to interfere with the large surfaces implicated in PPIs. Progress on peptide administration, stability, biodelivery and safety are also encouraging the interest in peptide drug development. The concept of IPs has been validated for several PPIs, generating great expectations for their therapeutic potential. Here, we describe approaches and methods useful for IPs identification and in silico, physicochemical and biological-based strategies for their design and optimization. Selected promising in-vivo-validated examples are described and advantages, limitations and potential of IPs as therapeutic tools are discussed.

引用

页码：272 / 285

页数：14

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