Transformation of peptides to small molecules in medicinal chemistry:Challenges and opportunities  

作　　者：Zeyu Han Zekai Shen Jiayue Pei Qidong You Qiuyue Zhang Lei Wang 

机构地区：[1]State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University,Nanjing 210009,China [2]Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第10期4243-4265,共23页药学学报（英文版）

基　　金：supported by projects 82173741 and 82304309 of the National Natural Science Foundation of China;BK20230103 and BK20231014 of the Natural Science Foundation of Jiangsu Province;Young Elite Scientists Sponsorship Program by CAST(2021QNRC001,China);China Postdoctoral Science Foundation(2022M723512);Fundamental Research Funds for the Central Universities(2632023GR13,China);Jiangsu Funding Program for Excellent Postdoctoral Talent(2023ZB429,China).

摘　　要：Peptides are native binders involved in numerous physiological life procedures,such as cellular signaling,and serve as ready-made regulators of biochemical processes.Meanwhile,small molecules compose many drugs owing to their outstanding advantages of physiochemical properties and synthetic convenience.A novel field of research is converting peptides into small molecules,providing a convenient portable solution for drug design or peptidomic research.Endowing properties of peptides onto small molecules can evolutionarily combine the advantages of both moieties and improve the biological druggability of molecules.Herein,we present eight representative recent cases in this conversion and elaborate on the transformation process of each case.We discuss the innovative technological methods and research approaches involved,and analyze the applicability conditions of the approaches and methods in each case,guiding further modifications of peptides to small molecules.Finally,based on the aforementioned cases,we summarize a general procedure for peptide-to-small molecule modifications,listing the technological methods available for each transformation step and providing our insights on the applicable scenarios for these methods.This review aims to present the progress of peptide-to-small molecule modifications and propose our thoughts and perspectives for future research in this field.

关 键 词：Small molecule PEPTIDE PEPTIDOMIMETICS Machine learning TRANSFORMATION MINIMIZATION Artificial intelligence 

分 类 号：R730.5[医药卫生—肿瘤]