期刊
CHEMBIOCHEM
卷 19, 期 10, 页码 1031-1035出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201800121
关键词
chemoselectivity; copper acetylide; Glaser; macrocyclization; peptide stapling
资金
- National Institutes of Health [NIH R01AI113867]
- Stichting Fundatie van de Vrijvrouwe van Renswoude [AV20170242]
Peptide macrocycles are widely utilized in the development of high affinity ligands, including stapled -helices. The linear rigidity of a 1,3-diynyl linkage provides an optimal distance (7 angstrom) between -carbons of the i,i+4 amino acid side chains, thus suggesting its utility in stabilizing -helical structures. Here, we report the development of an on-resin strategy for an intramolecular Glaser reaction between two alkyne-terminated side chains by using copper chloride, an essential bpy-diol ligand, and diisopropylethylamine at room temperature. The efficiency of this ligation was illustrated by the synthesis of (i,i+4)-, (i,i+5)-, (i,i+6)-, and (i,i+7)-stapled BCL-9 -helical peptides using the unnatural amino acid propargyl serine. Overall, this procedurally simple method relies on inexpensive and widely available reagents to generate low molecular weight 23-, 26-, 29-, and 32-membered peptide macrocycles.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据