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Updated: Jul 8, 2025

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使用聚焦的DNA编码化学库利用β-乳酸酶的碳酸盐结合口袋

Suhyeorn Park¹, Jiayi Fan¹, Srinivas Chamakuri²

¹Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, Texas 77030, United States.

Journal of medicinal chemistry

|December 20, 2023

概括

研究人员使用DNA编码化学库 (DECL) 技术发现了抗卡巴胺细菌的新型抑制剂. 这种方法针对β-乳酸酶酶.

科学领域:

微生物学微生物学
药用化学医学化学
药物发现药物发现药物发现

背景情况:

β-乳酸酶酶赋予细菌对β-乳酸抗生素的耐药性.
OXA-48和NDM-1β-乳酸酶对卡巴胺具有抗性,这对公众健康构成重大风险.
新型抑制剂对于对抗耐药细菌引起的感染至关重要.

研究的目的:

发现β-乳糖酶的新型抑制剂,特别是OXA-48和NDM-1.
为了利用DNA编码化学库 (DECL) 技术来发现抑制剂.
开发非β-乳糖酶的非β-乳糖酶药,准β-乳糖酶的保存的碳酸盐结合口袋.

主要方法:

设计和建造了一个由10^6个化合物组成的DNA编码化学库 (DECL).
针对基于酶基质结合相互作用的β-乳糖酶保存的碳酸盐结合口袋.
选了DECL以确定OXA-48和NDM-1β-乳酸酶的抑制剂.

主要成果:

鉴定了OXA-48和NDM-1β-乳糖酶抑制剂,具有微分子到纳米分子强度.
实现了NDM-1抑制剂的进一步优化,提高了它们的效能和生物活性.
通过DECL方法发现了新的非β-lactam药.

结论:

DNA编码化学库 (DECL) 技术对于发现β-乳糖酶抑制剂是有效的.
准碳酸盐结合口袋是广泛的β-lactamase抑制的可行策略.
鉴定到的新型药为开发抗耐药细菌的新抗生素提供了潜力.

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