Lead compound optimization strategy (7) —— modification strategies for peptides
10.16438/j.0513-4870.2019-0877
- VernacularTitle:先导化合物结构优化策略 (七) —— 肽类分子结构修饰与改造
- Author:
Jing-jing PENG
1
,
2
;
Jiang WANG
1
,
2
;
Wen-hao DAI
1
;
Xiong XIE
1
,
2
;
Hong LIU
1
,
2
Author Information
1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2. University of Chinese Academy of Sciences, Beijing 100049, China
- Publication Type:Research Article
- Keywords:
peptide;
structure optimization;
rug design;
lead compound
- From:
Acta Pharmaceutica Sinica
2020;55(3):427-445
- CountryChina
- Language:Chinese
-
Abstract:
Most peptides have high binding affinity and good selectivity for endogenous receptors and are good lead compounds to develop into drugs. Many approved drugs are derived from the structural optimization of peptide molecules, such as the antihypertensive drug captopril and the anti-hepatitis C drug telaprevir. At present, the main problems in the development of peptide drugs include poor stability, short half-life, and high plasma clearance rate; lack of oral availability and poor patient compliance, a complex production process, and high production cost. Therefore, rational modification of peptides can not only reduce the production cost, but also improve the druggability of the peptides. Here we review structural modification strategies for peptides from the perspective of improving their physicochemical properties. These modification strategies are divided into two parts: one is modification of the peptide backbone, including unnatural amino acid modification, pseudopeptide strategy, inverse-peptide strategy, cyclization strategy, and terminal structure modification. Another is modification of the side chains of peptides, including fatty acid conjugation, polyethylene glycol conjugation, protein fusion strategy, and cholesterol conjugation.
