Screening derivatized peptide libraries for tight binding inhibitors to carbonic anhydrase II by electrospray ionization mass spectrometry
Screening derivatized peptide libraries for tight binding inhibitors to carbonic anhydrase II by electrospray ionization mass spectrometry
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DOI：
10.1021/jm960013g
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发表时间：
1996-05-10
影响因子：
7.3
通讯作者：
Whitesides, GM
中科院分区：
文献类型：
--
作者：
Gao, JM;Cheng, XH;Whitesides, GM
本文介绍了使用电喷雾电离质谱（ESI-MS）筛选两个可溶性化合物库，以寻找碳酸酐酶II（EC 4.2.1.1）的紧密结合抑制剂。两个库H2 NO2 SC 6 H4 C（O）NH-AA（1）-AA（2）-C（O）NHCH 2CH 2CO 2 H（1），其中AA（1）和AA（2）是L-氨基酸（库大小：289种化合物）或D-氨基酸（256种化合物）通过将三肽连接到4-羧基苯磺酰胺的羧基上来构建。两个文库的筛选产生作为最紧密结合抑制剂的化合物1（AA（1）= AA（2）= L-Leu;结合常数K-b = 1.4 × 10（8）M（-1））。ESI-MS同时估计蛋白质与库中可溶性配体的相对结合亲和力的能力，如果通用的话，应该在药物开发中是有用的。
This paper describes the use of electrospray ionization-mass spectrometry (ESI-MS) to screen two libraries of soluble compounds to search for tight binding inhibitors for carbonic anhydrase II (EC 4.2.1.1). The two libraries, H2NO2SC6H4C(O)NH-AA(1)-AA(2)-C(O)NHCH2CH2CO2H (1), where AA(1) and AA(2) are L-amino acids (library size: 289 compounds) or D-amino acids (256 compounds), were constructed by attaching tripeptides to the carboxyl group of 4-carboxybenzenesulfonamide. Screening of both libraries yielded, as the tightest binding inhibitor, compound 1 (AA(1) = AA(2) = L-Leu; binding constant K-b = 1.4 X 10(8) M(-1)). The ability of ESI-MS to estimate simultaneously the relative binding affinities of a protein to soluble ligands in a library, if general, should be useful in drug development.