title: One-pot native chemical ligation of peptide hydrazides enables total synthesis of modified histones.
abstract: One of the rising demands in the field of protein chemical synthesis is the development of facile strategies that yield the protein in workable quantities and homogeneity, with fewer handling steps. Although the native chemical ligation of peptide hydrazides has recently been shown to be useful for the chemical synthesis of proteins carrying acid-sensitive modification groups, previous hydrazide-based protein synthesis studies have used sequential ligation strategies. Here, we report a practical method for a "one-pot" native chemical ligation of peptide hydrazides that would circumvent the need for the isolation of the intermediate products. This method employed a fast and selective arylboronate oxidation reaction mediated by H2O2, which draws attention to the potential applications of the thus far under-exploited boron-based functionalities in protein chemical synthesis. To demonstrate the practicality and efficiency of the new one-pot method, we report its application to a scalable total synthesis of modified histones (with five analogues of H3 and H4 as examples) on a multi-milligram scale, with good homogeneity.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, MOE Key Laboratory of Protein Sciences, Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Li
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Qiaoqiao
authors.initials: Q
authors.lastname: He
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D002625:Chemistry, Organic / Q000379:methods*; D006657:Histones / Q000138:chemical synthesis* / Q000737:chemistry; D006834:Hydrazines / Q000138:chemical synthesis*; D008239:Lysine / Q000378:metabolism; D013058:Mass Spectrometry; D008745:Methylation; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones; D006834:Hydrazines; D010455:Peptides; D008239:Lysine