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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Alternate protein frameworks for molecular recognition.
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Alternate protein frameworks for molecular recognition.

机译：用于分子识别的替代蛋白质框架。

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摘要

In an effort to determine whether proteins with structures other than the immunoglobulin fold can be used to mimic the ligand binding properties of antibodies, we generated a library from the four-helix bundle protein cytochrome b562 in which the two loops were randomized. Panning of this library against the bovine serum albumin (BSA) conjugate of N-methyl-p-nitrobenzylamine derivative 1 by phage display methods yielded cytochromes in which residues Trp-20, Arg-21, and Ser-22 in loop A and Arg-83 and Trp-84 in loop B were conserved. The individual mutants, which fold into native-like structure, bind selectively to the BSA-1 conjugate with micromolar dissociation constants (Kd), in comparison to a monoclonal antibody that binds selectively to 1 with a Kd of 290 nM. These and other antibody-like receptors may prove useful as therapeutic agents or as reagents for both intra- and extracellular studies.
机译：为了确定是否可以使用具有非免疫球蛋白折叠结构的蛋白来模拟抗体的配体结合特性，我们从四螺旋束蛋白细胞色素b562中生成了一个文库，其中两个环是随机的。通过噬菌体展示方法针对N-甲基-对-硝基苄胺衍生物1的牛血清白蛋白（BSA）偶联物淘选该文库，产生了细胞色素，其中在环A和Arg-中残基Trp-20，Arg-21和Ser-22 B环中的83和Trp-84是保守的。折叠成天然样结构的单个突变体，与以290 nM的Kd选择性结合1的单克隆抗体相比，具有微摩尔解离常数（Kd）的BSA-1缀合物选择性结合。这些和其他抗体样受体可被证明可用作治疗剂或细胞内和细胞外研究的试剂。

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