Engineered protein inhibitors for precise targeting of matrix metalloproteinases

IF 11 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Trends in Biochemical Sciences Pub Date : 2025-10-01 DOI:10.1016/j.tibs.2025.08.002

Naama Rotenberg , Noam Y. Bentolila , Julia M. Shifman

引用次数: 0

Abstract

Matrix metalloproteinases (MMPs) are a family of 23 zinc-dependent proteases involved in extracellular matrix (ECM) remodeling and are implicated in diseases such as cancer, arthritis, and cardiovascular disorders. Broad-spectrum MMP inhibitors (MMPIs) have proven counterproductive due to the protective roles of certain MMPs and their expression in healthy tissues. Recent advances in protein engineering have enabled the development of highly specific protein-based MMPIs that precisely target individual MMPs. These engineered proteins, often derived from antibody fragments or endogenous MMPIs, offer enhanced selectivity, reduced off-target effects, and improved therapeutic efficacy. This review highlights novel strategies for the precise targeting of MMPs using engineered proteins and discusses their potential to transform diagnostics and treatment of MMP-driven diseases.

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精确靶向基质金属蛋白酶的工程蛋白抑制剂。

基质金属蛋白酶（MMPs）是一个由23个锌依赖蛋白酶组成的家族，参与细胞外基质（ECM）重塑，并与癌症、关节炎和心血管疾病等疾病有关。由于某些MMP的保护作用及其在健康组织中的表达，广谱MMP抑制剂（MMPIs）已被证明是适得其反的。蛋白质工程的最新进展使得开发高度特异性的基于蛋白质的mmpi能够精确地靶向单个MMPs。这些工程蛋白通常来源于抗体片段或内源性mmpi，具有增强的选择性，减少脱靶效应，提高治疗效果。这篇综述强调了利用工程蛋白精确靶向MMPs的新策略，并讨论了它们在改变mmp驱动疾病的诊断和治疗方面的潜力。

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

Trends in Biochemical Sciences 生物-生化与分子生物学

CiteScore

22.90

自引率

0.70%

发文量

148

审稿时长

6-12 weeks

期刊介绍： For over 40 years, Trends in Biochemical Sciences (TIBS) has been a leading publication keeping readers informed about recent advances in all areas of biochemistry and molecular biology. Through monthly, peer-reviewed issues, TIBS covers a wide range of topics, from traditional subjects like protein structure and function to emerging areas in signaling and metabolism. Articles are curated by the Editor and authored by top researchers in their fields, with a focus on moving beyond simple literature summaries to providing novel insights and perspectives. Each issue primarily features concise and timely Reviews and Opinions, supplemented by shorter articles including Spotlights, Forums, and Technology of the Month, as well as impactful pieces like Science & Society and Scientific Life articles.