Lead discovery and optimization strategies for peptide macrocycles

被引：63
作者：
Bhat, Abhijit [1 ]
Roberts, Lee R. [2 ]
Dwyer, John J. [3 ]
机构：
[1] Ipsen Biosci Inc, Cambridge, MA 02142 USA
[2] Pfizer Worldwide Med Chem, Cambridge, MA 02140 USA
[3] Ferring Res Inst, San Diego, CA 92121 USA
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 94卷
关键词：
Peptides; Macrocycles; PPI; Phage display; mRNA display; CYCLIC-PEPTIDES; PHAGE DISPLAY; ALPHA-HELICES; IN-VIVO; DERIVATIVES; DESIGN; BIOAVAILABILITY; PERMEABILITY; SELECTION; PROTEINS;
D O I：
10.1016/j.ejmech.2014.07.083
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Peptide macrocycles represent a chemical space where the best of biological tools can synergize with the best of chemical approaches in the quest for leads against undruggable targets. Peptide macrocycles offer some key advantages in both lead discovery and lead optimization phases of drug discovery when compared to natural product and synthetic macrocycles. In addition, they are uniquely positioned to capitalize on the therapeutic potential of peptides because cyclization can help drive selectivity, potency and overcome the common limitations of metabolic instability of peptides. (C) 2014 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：471 / 479
页数：9
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