成纤维细胞活化蛋白的研究进展

成纤维细胞活化蛋白(fibroblast activation protein,FAP)是一种Ⅱ型跨膜丝氨酸蛋白水解酶,在多种内源性多肽及多肽类药物的代谢中起着至关重要的作用.在过去十年中,FAP已经被多个领域的研究人员广泛关注,包括生物化学、药学、临床医学等.随着对FAP生理功能及其与临床相关疾病发生发展关系研究的深入,FAP在人体内正常和相关疾病状态下的调控方式已经越发清晰.研究表明,FAP既可以作为肿瘤的潜在靶点,又可以作为肿瘤、类风湿性关节炎等疾病早期诊断的生物学标志物.因此,多种FAP的检测方法和抑制剂被相继报道.本综述总结近年来FAP的相关研究,立足于FAP结构特点、催化性能、内源底物特征及外源底物偏好性、组织分布和组织特异性、生物功能,分析当前FAP体外和体内的检测方法和抑制剂开发的优势与不足,总结FAP检测底物的结构特征和抑制剂的潜在构效关系.本综述将对FAP特异性检测方法和强效抑制剂的开发提供重要的参考价值.

Research Progress in Fibroblast Activation Protein

Over the past decade, fibroblast activation protein (FAP), a type II transmembrane serine hydrolase, has been identified and investigated widely in multiple research fields, including biochemistry, pharmacy, clinical medicine, which plays a key role in the metabolism of multiple endogenous peptides and peptide drugs. With the researching of FAP on its physiological functions and the relationships between FAP and clinical diseases, the biological or pathological processes of FAP in normal human or FAP-related diseases has been more clearer. Besides of being a potential therapeutic target for the treatment of cancer, FAP also serves as diagnostic markers for some diseases such as tumor and rheumatoid arthritis. Therefore, a variety of FAP detection methods and inhibitors have been reported. Based on FAP structural features, catalytic properties, endogenous substrate characteristics and exogenous substrate preferences, tissue distribution and specificity, and biological functions, this review not only analyzed the advantages and disadvantages of current FAP detection methods (in vitro and in vivo) and inhibitors but also summarized the structural characteristics of FAP detection substrates and the potential structure-activity relationship of inhibitors. This review will provide an overview of reference values and important reference value for the development of FAP-specific detection methods and potent inhibitors.