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通过体外选择发现的合成配体

S Jarrett Wrenn¹, Rebecca M Weisinger, David R Halpin

¹Department of Biochemistry, Stanford University, Stanford, California 94305, USA.

Journal of the American Chemical Society

|October 9, 2007

概括

进化策略可以发现新的小分子配体. 用DNA编程的化学产生了1亿种化合物,为Crk SH3域识别了具有高亲和力的新结合物.

科学领域:

生物化学生物化学
分子生物学分子生物学
药物发现药物发现药物发现

背景情况:

生物聚合物的功能性质来自进化和体外仿真.
用DNA编程合成为进化小分子发现提供了潜力.

研究的目的:

测试小分子发现进化策略的可行性.
为了确定原型瘤基因Crk.N-终端SH3域的新型配体.

主要方法:

利用DNA编程的组合化学合成了1亿种不同的化合物.
在六代人中应用了进化选择过程.
选的化合物与Crk SH3域结合.

主要成果:

聚合的分子群体产生了新的SH3域连接体.
识别的配体表现出与配体相似的结合亲和力.
在小分子发现中证明了进化方法的成功应用.

结论:

进化策略是有效的发现高亲和小分子连接体.
用DNA编程的化学加速和简化了小分子的发现.
这种方法对未来的药物发现工作具有重大潜力.

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