Investigation of protein post-translational modifications with site-specifically incorporated non-canonical amino acids

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.

Keywords: Genetic code expansion; Non-canonical amino acids; Protein post-translational modifications.