Luo Yining, Gao Jingchun, Jiang Xukai, Zhu Ling, Zhou Qi Tony, Murray Michael, Li Jian, Zhou Fanfan
Molecular Drug Development Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney 2006, Australia.
National Glycoengineering Research Center, Shandong University, Qingdao 266237, China.
Pharmaceutics. 2023 Oct 23;15(10):2517. doi: 10.3390/pharmaceutics15102517.
Human proton-coupled oligopeptide transporters (PepTs) are important membrane influx transporters that facilitate the cellular uptake of many drugs including ACE inhibitors and antibiotics. PepTs mediate the absorption of di- and tri-peptides from dietary proteins or gastrointestinal secretions, facilitate the reabsorption of peptide-bound amino acids in the kidney, and regulate neuropeptide homeostasis in extracellular fluids. PepT1 and PepT2 have been the most intensively investigated of all PepT isoforms. Modulating the interactions of PepTs and their drug substrates could influence treatment outcomes and adverse effects with certain therapies. In recent studies, topology models and protein structures of PepTs have been developed. The aim of this review was to summarise the current knowledge regarding structure-interaction relationships (SIRs) of PepTs and their substrates as well as the potential applications of this information in therapeutic optimisation and drug development. Such information may provide insights into the efficacy of PepT drug substrates in patients, mechanisms of drug-drug/food interactions and the potential role of PepTs targeting in drug design and development strategies.
人类质子偶联寡肽转运体（PepTs）是重要的膜内向转运体，可促进包括ACE抑制剂和抗生素在内的多种药物的细胞摄取。PepTs介导膳食蛋白质或胃肠道分泌物中双肽和三肽的吸收，促进肾脏中肽结合氨基酸的重吸收，并调节细胞外液中的神经肽稳态。PepT1和PepT2是所有PepT亚型中研究最为深入的。调节PepTs与其药物底物之间的相互作用可能会影响某些治疗的治疗效果和不良反应。在最近的研究中，已经建立了PepTs的拓扑模型和蛋白质结构。本综述的目的是总结关于PepTs及其底物的结构-相互作用关系（SIRs）的当前知识，以及这些信息在治疗优化和药物开发中的潜在应用。此类信息可能有助于深入了解PepT药物底物在患者中的疗效、药物-药物/食物相互作用的机制以及PepTs靶向在药物设计和开发策略中的潜在作用。
