Selvaraj Anand, Chen Hui-Ting, Ya-Ting Huang Adela, Kao Chai-Lin
Department of Medicinal and Applied Chemistry , Kaohsiung Medical University , Kaohsiung 807 , Taiwan . Email:
Department of Fragrance and Cosmetic Science , Kaohsiung Medical University , Kaohsiung 807 , Taiwan.
Chem Sci. 2017 Oct 30;9(2):345-349. doi: 10.1039/c7sc03229c. eCollection 2018 Jan 14.
A convenient and efficient chemical toolbox was developed for the on-resin C-terminal functionalization of various peptides. By transforming resin-bound 3,4-diaminobenzoic acid species with isoamyl nitrite, the resulting resin-bound benzotriazole entity can be efficiently displaced by nucleophiles during cleavage of the peptide-resin connection in a short reaction time. The resin cleavage step allowed for the use of various nucleophiles including water, EtOH, amines, thiol, and G5 poly(amidoamino) dendrimers with yields ranging from 66% to 82% within 5 h. This method was successfully applied to prepare the elastin sequence (VPGVG) through on-resin ligation in 77% yield in one day and a head-to-tail cyclic peptide, sunflower trypsin inhibitor-1, in 42% yield.
开发了一种方便高效的化学工具箱，用于各种肽的树脂上C端功能化。通过用异戊基亚硝酸酯转化树脂结合的3,4-二氨基苯甲酸物种，在短反应时间内肽-树脂连接的裂解过程中，所得树脂结合的苯并三唑实体可被亲核试剂有效取代。树脂裂解步骤允许使用各种亲核试剂，包括水、乙醇、胺、硫醇和G5聚（酰胺氨基）树枝状大分子，在5小时内产率范围为66%至82%。该方法成功应用于通过树脂上连接以77%的产率在一天内制备弹性蛋白序列（VPGVG），以及以42%的产率制备头对尾环肽向日葵胰蛋白酶抑制剂-1。
