二肽基肽酶IV的测定技术及其抑制剂的筛选
Techniques for the determination of dipeptidyl peptidase IV and screening of its inhibitors.
摘要(中文译文)
二肽基肽酶IV（DPP-IV）是丝氨酸水解酶家族的重要成员，因其独特的广谱底物特异性，在多种生理和病理过程中发挥核心调控作用。DPP-IV介导的内源性肽底物蛋白水解加工作为调控生理过程的基本机制。深入探究DPP-IV活性的酶学特征及调控机制，不仅能为揭示相关疾病的分子发病机制提供理论基础，也有助于构建完整的疾病调控网络图谱。此外，开发特异性DPP-IV抑制剂是创新治疗的关键策略，具有重要的临床转化前景。本综述全面比较了DPP-IV在信使RNA（mRNA）、蛋白质和功能水平检测中的应用、优势与局限性，并深入分析了DPP-IV酶活性评估如何深刻影响疾病发病机制、进展及治疗干预。特别强调了基于药物和光学底物（如用于荧光和生物发光）的探针在DPP-IV功能测定中的优越性能。通过代谢表型分析，我们进一步总结了跨多个生物学层面靶向DPP-IV的药物筛选体系，包括重组蛋白（如来源于人类、动物及 的蛋白质）、组织、细胞、人器官芯片模型及整体动物研究。此外，本综述全面评估了合成和天然DPP-IV抑制剂。同时，对其构效关系（SARs）的系统研究为开发具有更高疗效和安全性的新型抑制剂提供了合理基础。
Abstract
Dipeptidyl peptidase IV (DPP-IV), an important member of the serine hydrolase family, plays a core regulatory role in various physiological and pathological processes because of its unique broad-spectrum substrate specificity. DPP-IV-mediated proteolytic processing of endogenous peptide substrates serves as a fundamental regulatory mechanism governing physiological processes. An in-depth exploration of the enzymatic characteristics and mechanisms regulating DPP-IV activity will not only provide a theoretical basis for revealing the molecular pathogenesis of related diseases but also contribute to the construction of a complete disease regulatory network map. Furthermore, the development of specific DPP-IV inhibitors constitutes a key strategy for innovative therapy, holding significant promise for clinical translation. This review provides a comprehensive comparison of the applications, merits, and limitations of DPP-IV detection at the messenger RNA (mRNA), protein, and functional levels, along with an in-depth analysis of how DPP-IV enzymatic activity assessment profoundly impacts disease pathogenesis, progression, and therapeutic interventions. Particular emphasis is placed on the superior performance of probes based on drugs and optical substrates (e.g., for fluorescence and bioluminescence) in the functional determination of DPP-IV. Through metabolic phenotyping, we further summarize drug screening systems that target DPP-IV across multiple biological levels, including recombinant proteins (e.g., proteins derived from humans, animals, and ), tissues, cells, human organ-on-a-chip models, and whole-animal studies. Furthermore, this review comprehensively evaluates both synthetic and natural DPP-IV inhibitors. Additionally, systematic investigations of their structure-activity relationships (SARs) provide a rational foundation for developing novel inhibitors with enhanced efficacy and safety.
如何引用
AMA
Hong-Hong Ma, Xiao-Dong Li, Xing-Kai Qian, Li-Wei Zou. Techniques for the determination of dipeptidyl peptidase IV and screening of its inhibitors.. Journal of pharmaceutical analysis. 2026; doi:10.1016/j.jpha.2025.101499.
APA
Hong-Hong Ma, Xiao-Dong Li, Xing-Kai Qian, Li-Wei Zou (2026). Techniques for the determination of dipeptidyl peptidase IV and screening of its inhibitors.. Journal of pharmaceutical analysis. https://doi.org/10.1016/j.jpha.2025.101499
GB/T 7714
Hong-Hong Ma, Xiao-Dong Li, Xing-Kai Qian, Li-Wei Zou. Techniques for the determination of dipeptidyl peptidase IV and screening of its inhibitors.[J]. Journal of pharmaceutical analysis, 2026 doi:10.1016/j.jpha.2025.101499.
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