CYCLIC PEPTIDES
    3.
    发明申请
    CYCLIC PEPTIDES 有权
    循环肽

    公开(公告)号:US20070207502A1

    公开(公告)日:2007-09-06

    申请号:US11670112

    申请日:2007-02-01

    摘要: Methods of producing cyclic peptides and splicing intermediates of peptides in a looped conformation are disclosed. The methods utilize the trans-splicing ability of split inteins to catalyze cyclization of peptides from a precursor peptide having a target peptide interposed between two portions of a split intein. The interaction of the two portions of the split intein creates a catalytically-active intein and also forces the target peptide into a loop configuration that stabilizes the ester isomer of the amino acid at the junction between one of the intein portions and the target peptide. A heteroatom from the other intein portion then reacts with the ester to form a cyclic ester intermediate. The active intein catalyzes the formation of an aminosuccinimide that liberates a cyclized form of the target peptide, which spontaneously rearranges to form the thermodynamically favored backbone cyclic peptide product. Also disclosed are nucleic acid molecules, polypeptides, methods for making cyclic peptides, methods of making libraries, and methods of screening peptides.

    摘要翻译: 公开了以循环构象形成肽的环肽和剪接中间体的方法。 所述方法利用分裂内蛋白的转拼能力来催化来自前导肽的肽的环化,所述肽的前导肽插入分裂的内含肽的两部分之间。 分裂内含肽的两部分的相互作用产生催化活性内含肽,并且还将目标肽强制成使得在内含肽部分和目标肽之间的连接处稳定氨基酸的酯异构体的环构型。 来自另一个内含肽部分的杂原子然后与酯反应以形成环状酯中间体。 活性内含肽催化氨基琥珀酰亚胺的形成,其释放环化形式的靶肽,其自发重排以形成热力学上有利的主链环肽产物。 还公开了核酸分子,多肽,制备环肽的方法,制备文库的方法和筛选肽的方法。