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对人类EGFR进行宏循环d/l混合的体外选择

Sayaka Imanishi¹, Takayuki Katoh¹, Yizhen Yin¹

¹Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Journal of the American Chemical Society

|April 6, 2021

概括

研究人员开发了一种创新的方法来创建d/l混合的大型库. 这一突破使得新的蛋白质相互作用抑制剂 (PPI) 的发现成为可能,特别是针对人体表皮生长因子受体 (EGFR).

科学领域:

生物化学
医学化学
分子生物学

背景情况:

与传统的l-氨基酸相比,D/L混合具有更高的蛋白质溶解稳定性和结构多样性.
由于图书馆建设和活动选方面的挑战,开发新的d/l混合已受到阻碍.

研究的目的:

建立一个有效的方法来构建高度多样化的宏循环d/l混合.
证明这种方法在识别新型蛋白质相互作用抑制剂 (PPI) 中的有用性.

主要方法:

构建一个大规模的库 (10^12个成员) 的宏循环d/l混合,包含五种不同的d-氨基酸.
使用稀释中的快速选 (RaPID) 技术对特定的蛋白质选库.

主要成果:

成功生成了一个多样化的宏循环d/l混合.
通过使用RaPID选择对人体表皮生长因子受体 (EGFR) 进行了蛋白与蛋白相互作用 (PPI) 抑制剂的鉴定.

结论:

开发的方法为构建多种d/l混合库提供了可靠的方法.
这项进展有助于发现基于d/l混合的新疗法,包括针对EGFR等目标的PPI抑制剂.

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