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“拼接式”药物发现。基于细胞的骨架环化多肽基因编码文库的表达与筛选。

"Splicing up" drug discovery. Cell-based expression and screening of genetically-encoded libraries of backbone-cyclized polypeptides.

作者信息

Sancheti Harshkumar, Camarero Julio A

机构信息

Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90033, USA.

出版信息

Adv Drug Deliv Rev. 2009 Sep 30;61(11):908-17. doi: 10.1016/j.addr.2009.07.003. Epub 2009 Jul 21.

Abstract

The present paper reviews the use of protein splicing for the biosynthesis of backbone cyclic polypeptides. This general method allows the in vivo and in vitro biosynthesis of cyclic polypeptides using recombinant DNA expression techniques. Biosynthetic access to backbone cyclic peptides opens the possibility to generate cell-based combinatorial libraries that can be screened inside living cells for their ability to attenuate or inhibit cellular processes thus providing a new way for finding therapeutic agents.

摘要

本文综述了蛋白质剪接在主链环肽生物合成中的应用。这种通用方法允许使用重组DNA表达技术在体内和体外生物合成环肽。通过生物合成途径获得主链环肽为生成基于细胞的组合文库开辟了可能性,这些文库可在活细胞内进行筛选,以检测其减弱或抑制细胞过程的能力,从而为寻找治疗药物提供了一种新方法。

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本文引用的文献

1
Chemical Synthesis of a Circular Protein Domain: Evidence for Folding-Assisted Cyclization.环状蛋白质结构域的化学合成:折叠辅助环化的证据。
Angew Chem Int Ed Engl. 1998 Feb 16;37(3):347-349. doi: 10.1002/(SICI)1521-3773(19980216)37:3<347::AID-ANIE347>3.0.CO;2-5.
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Protease-catalysed protein splicing: a new post-translational modification?
Trends Biochem Sci. 2008 Aug;33(8):363-8. doi: 10.1016/j.tibs.2008.04.016. Epub 2008 Jul 1.
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Native chemical ligation of polypeptides.多肽的天然化学连接
Curr Protoc Protein Sci. 2001 May;Chapter 18:Unit18.4. doi: 10.1002/0471140864.ps1804s15.
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N-terminal cysteinyl proteins can be prepared using thrombin cleavage.N 端半胱氨酸蛋白可通过凝血酶切割制备。
FEBS Lett. 2008 Apr 2;582(7):1163-7. doi: 10.1016/j.febslet.2008.02.078. Epub 2008 Mar 10.
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Biosynthesis of circular proteins in plants.植物中环状蛋白质的生物合成。
Plant J. 2008 Feb;53(3):505-15. doi: 10.1111/j.1365-313X.2007.03357.x. Epub 2007 Dec 12.

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