Department of Chemistry, Washington State University, Pullman, Washington 99164-4630, USA.
J Am Chem Soc. 2011 Dec 21;133(50):20033-5. doi: 10.1021/ja207133t. Epub 2011 Nov 23.
A synthesis of aziridine-containing peptides via the Cu(II)-promoted coupling of unprotected peptide thioacids and N-H aziridine-2-carbonyl peptides is reported. The unique reactivity of the resulting N-acylated aziridine-2-carbonyl peptides facilitates their subsequent regioselective and stereoselective nucleophilic ring-opening to give unprotected peptides that are specifically modified at the ligation site. The aziridine-mediated peptide ligation concept is exemplified using H(2)O as the nucleophile, producing a Xaa-Thr linkage (where Xaa can be an epimerizable and hindered amino acid). The overall process is compatible with a variety of unprotected amino acid functionality, most notably the N-terminal and Lys side chain amines.
通过无保护的肽硫代羧酸和 N-H 氮丙啶-2-甲酰基肽的 Cu(II)促进偶联，合成了含氮丙啶的肽。所得 N-酰化氮丙啶-2-甲酰基肽的独特反应性有利于其随后进行区域选择性和立体选择性亲核开环，得到在连接位点特异性修饰的无保护肽。氮丙啶介导的肽连接概念通过使用 H2O 作为亲核试剂进行了举例说明，生成 Xaa-Thr 键（其中 Xaa 可以是可差向异构化和受阻的氨基酸）。该过程与各种未保护氨基酸官能团相容，特别是 N-末端和赖氨酸侧链胺。
