TCP-1,a novel peptide to diagnose early colon cancer  

作　　者：Hang Yu Baoying Wen Min Huang Ru Feng Libin Pan Manyi Xu Hao Lin Lin Cong Sen Zhang Yan Li Chi-Hin Cho Chongjing Zhang Xiaoguang Chen Yan Wang 

机构地区：[1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing 100050,China [2]School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong,China

出　　处：《Chinese Chemical Letters》2024年第3期226-233,共8页中国化学快报（英文版）

基　　金：supported by the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2021-I2M-1-027);National Natural Science Foundation of China(Nos.T2192972,81402997);Key Project of Beijing Natural Science Foundation(No.7181007);National High-tech Research and Development Plan(863 Plan,No.2014AA020803);Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study(No.Z141102004414062)。

摘　　要：A nine cyclic peptide(TCP-1)showed excellent specificity for colon cancer.TCP-1 binds with human tumor tissues at early stages and mice tumor with diameters of 1-4 mm,suggesting that TCP-1 may be used for early diagnosis of colon cancer.The mechanism of the targeted binding of TCP-1 to colon cancer was also studied using immunoprecipitation,LC-MS and bioinformatics.After screening and identifying of the possible binding target proteins of TCP-1,keratin,typeⅡcytoskeletal 5 was speculated to be the specific binding target protein of TCP-1 in human tumor tissue.Pharmacokinetics studies were conducted to investigate the target-mediated drug disposition of the new tumor-specific peptide by LC-MS/MS.The tissue distribution study showed that TCP-1 was found only in colon tumors(the target site)in tumor mice did not bind to any other tissues.Conjugating TCP-1 to tumor markedly increased its removal rate from blood circulation but mildly extended its staying time in vivo.In tumor mice,a lower AUC of TCP-1(reduced by almost 35%)and 2-fold higher clearance were found compared to that of normal mice.The proposed metabolic pathway of TCP-1 in the kidney was also determined using LC-MS^(n)-IT-TOF.The high specificity and low toxicity of the peptide may be caused by its extremely tight binding to the targets.Potential applications for future clinical use,including MRI and PET/CT were also explored,and this research may promote the development of colon cancer diagnostic technology research and provide new ideas and technical routes for tumor diagnostic technology.

关 键 词：Colon cancer TCP-1 PEPTIDE Cytokeratin 5 Pharmacokinetics/pharmacodynamics(PK/PD) 

分 类 号：R735.35[医药卫生—肿瘤]