Realizing Serine/Threonine Ligation: Scope and Limitations and Mechanistic Implication Thereof

• 出版年: Frontiers in Chemistry
• 主要な著者: Clarence T. T. Wong, Tianlu eLi, Hiu Yung eLam, Yinfeng eZhang, Xuechen eLI
• フォーマット: 論文
• 言語: 英語
• 出版事項: Frontiers Media S.A. 2014-05-01
• 主題: protein synthesis; solid phase peptide synthesis; Peptide Ligation; Chemoselectivity; Peptide synthesis.
• オンライン･アクセス: http://journal.frontiersin.org/Journal/10.3389/fchem.2014.00028/full

Serine/Threonine ligation (STL) has emerged as an alternative tool for protein chemical synthesis, bioconjugations as well as macrocyclization of peptides of various sizes. Owning to the high abundance of Ser/Thr residues in natural peptides and proteins, STL is expected to find a wide range of applications in chemical biology research. Herein, we have fully investigated the compatibility of the serine/threonine ligation strategy for X-Ser/Thr ligation sites, where X is any of the 20 naturally occurring amino acids. Our studies have shown that 17 amino acids are suitable for ligation, while Asp, Glu, and Lys are not compatible. Among the working 17 C-terminal amino acids, the retarded reaction resulted from the bulky β-branched amino acid (Thr, Val and Ile) is not seen under the current ligation condition. We have also investigated the chemoselectivity involving the amino group of the internal lysine which may compete with the N-terminal Ser/Thr for reaction with the C-terminal salicylaldehyde (SAL) ester aldehyde group. The result suggested that the free internal amino group does not adversely slow down the ligation rate.