Herein, we report selection, synthesis, and enzymatic evaluation of a peptidomimetic library able to increase proteolytic activity of HtrA3 (high temperature requirement A) protease. Iterative deconvolution in solution of synthesized modified pentapeptides yielded two potent HtrA3 activators acting in the micromolar range (HCOO-CH₂O-C₆H₄-OCH₂-CO-Tyr-Asn-Phe-His-Asn-OH and HCOO-CH₂O-C₆H₄-OCH₂-CO-Tyr-Asn-Phe-His-Glu-OH). Both compounds increased proteolysis of an artificial HtrA3 substrate over 40-fold in a selective manner. On the basis of molecular modeling, the selected compounds bind strongly to the PDZ domain.

中文翻译：

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使用组合化学选择有效的HTRA3激活剂

在此，我们报告了能够提高HtrA3（高温要求A）蛋白酶的蛋白水解活性的拟肽文库的选择，合成和酶促评估。合成修饰五肽溶液中的迭代解卷积产生了两个有效的HtrA3激活剂，它们在微摩尔范围内起作用（HCOO-CH ₂ O-C ₆ H ₄ -OCH ₂ -CO-Tyr-Asn-Phe-His-Asn-OH和HCOO-CH ₂ O-C ₆ H ₄ -OCH ₂ -CO-Tyr-Asn-Phe-His-Glu-OH）。两种化合物均以选择性方式使人工HtrA3底物的蛋白水解增加40倍以上。在分子建模的基础上，所选化合物与PDZ结构域牢固结合。