Zhang Chi, Dai Peng, Spokoyny Alexander M, Pentelute Bradley L
Department of Chemistry, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
Org Lett. 2014 Jul 18;16(14):3652-5. doi: 10.1021/ol501609y. Epub 2014 Jul 8.
A glutathione S-transferase (GST) catalyzed macrocyclization reaction for peptides up to 40 amino acids in length is reported. GST catalyzes the selective S(N)Ar reaction between an N-terminal glutathione (GSH, γ-Glu-Cys-Gly) tag and a C-terminal perfluoroaryl-modified cysteine on the same polypeptide chain. Cyclic peptides ranging from 9 to 24 residues were quantitatively produced within 2 h in aqueous pH = 8 buffer at room temperature. The reaction was highly selective for cyclization at the GSH tag, enabling the combination of GST-catalyzed ligation with native chemical ligation to generate a large 40-residue peptide macrocycle.
报道了一种谷胱甘肽S-转移酶（GST）催化的、适用于长度达40个氨基酸的肽的大环化反应。GST催化同一多肽链上N端谷胱甘肽（GSH，γ-谷氨酰-半胱氨酰-甘氨酸）标签与C端全氟芳基修饰的半胱氨酸之间的选择性亲核芳香取代反应。在室温下的pH = 8的水性缓冲液中，9至24个残基的环肽在2小时内定量生成。该反应对GSH标签处的环化具有高度选择性，使得GST催化的连接与天然化学连接相结合，能够生成一个含40个残基的大型肽大环。
