{"title":"Investigation of protein post-translational modifications with site-specifically incorporated non-canonical amino acids","authors":"Jiayu Gu , Lihui Lao , Yulin Chen , Shixian Lin","doi":"10.1016/j.bmc.2024.118013","DOIUrl":null,"url":null,"abstract":"<div><div>Despite the important functions of protein post-translational modifications (PTMs) in numerous cellular processes, understanding the biological roles of PTMs remains quite challenging. Here, we summarize our efforts in recent years to incorporate a variety of non-canonical amino acids (ncAAs) to study the biological functions of protein PTMs in mammalian cells, with a focus on the use of ncAA tools to probe the biological functions of various protein PTMs. We design length-tunable lipidation mimics for studying lipidation function and designing protein drugs. We highlight the use of genetically encoded lysine aminoacylations as chemical baits to identify aminoacylated lysine ubiquitination. Finally, we discuss the use of genetically encoded electron-rich Trp derivatives to design binding affinity-enhancing histone methylations readers.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"117 ","pages":"Article 118013"},"PeriodicalIF":3.3000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0968089624004279","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Despite the important functions of protein post-translational modifications (PTMs) in numerous cellular processes, understanding the biological roles of PTMs remains quite challenging. Here, we summarize our efforts in recent years to incorporate a variety of non-canonical amino acids (ncAAs) to study the biological functions of protein PTMs in mammalian cells, with a focus on the use of ncAA tools to probe the biological functions of various protein PTMs. We design length-tunable lipidation mimics for studying lipidation function and designing protein drugs. We highlight the use of genetically encoded lysine aminoacylations as chemical baits to identify aminoacylated lysine ubiquitination. Finally, we discuss the use of genetically encoded electron-rich Trp derivatives to design binding affinity-enhancing histone methylations readers.
期刊介绍:
Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides.
The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.