文献类型：期刊文献

英文题名：Cryptand-imidazolium supported total synthesis of the lasso peptide BI-32169 and its D-enantiomer

作者：Chen, Ming[1];Wang, Shuanglong[2];Yu, Xihan[3]

机构：[1]Yanan Univ, Coll Life Sci, Lab Nat Peptide Chem, Shendi Rd 580, Yanan 716000, Peoples R China;[2]UPPA, CNRS, Lab Chim Analyt Bioinorgan & Environm, UMR5254, Helioparc,2,Ave Angot, F-64053 Pau, France;[3]East China Univ Sci & Technol, Coll Pharm, Meilong Rd 130, Shanghai 200237, Peoples R China

年份：2019

卷号：55

期号：23

起止页码：3323

外文期刊名：CHEMICAL COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000461397500025)】；

基金：S.-L. Wang thanks the China Scholarship Council for supporting his study in France. We appreciate Dr Maeda Suzuki (Hokkaido College of Pharmacy) for providing a sample of the native BI-32169 and Dr Martin Schlesinger (University Bonn) for proofreading the article. The Research Fund of the European Patent Organization and the State Intellectual Property Office of China are also acknowledged for partial financial support.

语种：英文

摘要：Lasso peptides are attracting increasing attention due to their broad range of biological activities. The knot topology of lasso peptides, which contains an isopeptide bond-bridged macrocycle threaded by its C-terminal tail, has been proven to be an important structural feature for their bioactivities. The preparation of lasso peptides has been achieved by biosynthetic methods; nevertheless, a chemical synthesis of lasso peptides has not been described so far. Herein, a cryptand-imidazolium complex is designed as a multi-linker support and applied in the chemical synthesis of the lasso peptide BI-32169. Furthermore, the chiral switching of the support and the introduction of D-amino acids enable the synthesis of the D-enantiomer of BI-32169, which shows not only a strong glucagon receptor antagonist activity, but also a much higher enzymatic stability compared to the L-lasso peptide.