School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland, 1142, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, School of Biological Sciences, The University of Auckland, Auckland, 1142, New Zealand.
Angew Chem Int Ed Engl. 2018 Sep 3;57(36):11640-11643. doi: 10.1002/anie.201805208. Epub 2018 Aug 6.
We report a new method herein coined SP-CLipPA (solid-phase cysteine lipidation of a peptide or amino acid) for the synthesis of mono-S-lipidated peptides. This technique utilizes thiol-ene chemistry for conjugation of a vinyl ester to a free thiol of a semiprotected, resin-bound peptide. Advantages of SP-CLipPA include: ease of handling, conversions of up to 91 %, by-product removal by simple filtration, and a single purification step. Additionally, the desired lipidated products show high chromatographic separation from impurities, thus facilitating RP-HPLC purification. To showcase the utility of SP-CLipPA, we synthesized a potent calcitonin gene-related peptide (CGRP) receptor antagonist peptide in excellent yield and purity. This peptide, selected from a series of lipidated analogues of CGRP and CGRP , has potential for the treatment of migraine.
我们在此报告一种新方法，称为 SP-CLipPA（肽或氨基酸的固相半胱氨酸脂化），用于合成单脂肽。该技术利用硫醇-烯反应将乙烯酯与半保护的树脂结合的肽的游离巯基连接。SP-CLipPA 的优点包括：易于处理、转化率高达 91%、通过简单过滤去除副产物以及单一的纯化步骤。此外，所需的脂化产物与杂质有很好的色谱分离，因此有利于反相高效液相色谱纯化。为了展示 SP-CLipPA 的实用性，我们以优异的收率和纯度合成了一种有效的降钙素基因相关肽（CGRP）受体拮抗剂肽。该肽是从一系列 CGRP 和 CGRP 的脂化类似物中筛选出来的，具有治疗偏头痛的潜力。
