Synthesis of substrate peptides incorporating non-natural amino acids and screening study using BACE1

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-05-28 DOI:10.1016/j.bmcl.2025.130290

Shinji Katsuoka, Ryo Watanabe, Yuma Uchida, Masaki Midorikawa, Reo Yamada, Taeko Kakizawa

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引用次数: 0

Abstract

Peptide library screening is used to detect optimal sequences for enzymatic cleavage; moreover, the data obtained through this screening are useful for the establishment of a fast screening system and designing of substrate-based enzyme inhibitors. In this study, peptide libraries were prepared and digested with the beta-site amyloid precursor protein cleaving enzyme (BACE1). BACE1 has been used as a target enzyme for drug development against Alzheimer's disease (AD). The library sequences were derived from our previous screening study based on amyloid-beta precursor protein (APP) substrates. Then, newly selected non-natural amino acids were incorporated into several positions on these sequences. After digestion with BACE1, the reaction mixtures were analyzed with high-performance liquid chromatography followed by mass spectrometry to identify the peptides undergoing efficient cleavage. The data obtained from this study can be used for designing drugs against AD in the future.

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含非天然氨基酸的底物肽的合成及BACE1筛选研究。

肽库筛选用于检测酶促裂解的最佳序列；此外，通过该筛选获得的数据对于建立快速筛选系统和设计基于底物的酶抑制剂具有重要意义。本研究制备了肽库，并用β位点淀粉样蛋白前体蛋白切割酶（BACE1）进行酶切。BACE1已被用作阿尔茨海默病（AD）药物开发的靶酶。该文库序列来源于我们之前基于淀粉样蛋白前体蛋白（APP）底物的筛选研究。然后，将新选择的非天然氨基酸整合到这些序列的几个位置上。用BACE1消化后，用高效液相色谱和质谱分析反应混合物，以鉴定有效裂解的肽段。本研究获得的数据可用于未来针对AD的药物设计。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.