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目的综述人寡肽转运体1(hPepT1)的结构特点、功能、在生物体内的分布和调控,及其底物的结构特征。方法通过对国内外近年来对寡肽转运体研究的调研,归纳总结hPepT1的研究现状。结果hPepT1除转运饮食中二肽/三肽外,在拟肽类药物的摄取中也起关键的作用,如对β-内酰胺类抗生素及血管紧张素转换酶抑制剂的吸收。hPepT1主要在小肠表达,并受多种因素,如激素,表皮生长因子,饮食,疾病等调控。以hPepT1为靶点,对药物进行结构修饰设计前药,以提高母体药物的口服生物利用度是非常有潜力的策略,目前已有许多成功的例子。由于hPepT1的晶体结构尚没有完全阐明,研究者通过各种体内外模型的转运摄取实验,获得了很多关于hPepT1对底物结构要求的信息。结论通过文献调研,综述了hPepT1结构特点、功能、在生物体内的分布和调控,尤其是其底物的结构特征,强调其在前药设计中的应用。
OBJECTIVE: To review the structural features, functions, distribution and regulation of hPepT1 in human beings and the structural characteristics of hPepT1. Methods Based on the investigation of oligopeptide transporters at home and abroad in recent years, the research status of hPepT1 was summarized. Results hPepT1 plays a pivotal role in the uptake of peptidomimetics in addition to the dipeptide / tripeptide in the diet, such as the absorption of β-lactam antibiotics and angiotensin-converting enzyme inhibitors. hPepT1 is mainly expressed in the small intestine and is regulated by many factors such as hormones, epidermal growth factors, diet, diseases and the like. Taking hPepT1 as a target, the structural modification of drugs to design prodrugs to improve the oral bioavailability of the parent drug is a potential strategy. There are many successful examples. Since the crystal structure of hPepT1 has not been fully elucidated, researchers have obtained a lot of information about the substrate structure requirement of hPepT1 through various in vitro and in vivo uptake assays. Conclusion Through literature review, the structural features, functions, distribution and regulation of hPepT1 in vivo, especially the structural features of hPepT1, were summarized. The application of hPepT1 in prodrug design was emphasized.