Pauff Steven M, Fallows Andrew J, Mackay Simon P, Su Wu, Cullis Paul M, Burley Glenn A
Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, United Kingdom.
Department of Chemistry, University of Leicester, Leicester, United Kingdom.
Curr Protoc Nucleic Acid Chem. 2015 Dec 1;63:8.10.1-8.10.41. doi: 10.1002/0471142700.nc0810s63.
Pyrrole-imidazole polyamides (PAs) are a family of DNA-binding peptides that bind in the minor groove of double-stranded DNA (dsDNA) in a sequence-selective, programmable fashion. This protocol describes a detailed manual procedure for the solid-phase synthesis of this family of compounds. The protocol entails solution-phase synthesis of the Boc-protected pyrrole (Py) and imidazole (Im) carboxylic acid building blocks. This unit also describes the importance of choosing the appropriate condensing agent to form the amide linkages between each building block. Finally, a monomeric coupling protocol and a fragment-based approach are described that delivers PAs in 13% to 30% yield in 8 days.
吡咯-咪唑聚酰胺（PAs）是一类DNA结合肽，它们以序列选择性、可编程的方式结合于双链DNA（dsDNA）的小沟中。本方案描述了该类化合物固相合成的详细手动操作程序。该方案需要对Boc保护的吡咯（Py）和咪唑（Im）羧酸构建块进行溶液相合成。本单元还描述了选择合适的缩合剂以形成各构建块之间酰胺键的重要性。最后，描述了一种单体偶联方案和一种基于片段的方法，该方法可在8天内以13%至30%的产率得到PAs。
