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

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

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A nine cyclic peptide(TCP-1)showed excellent specificity for colon cancer.TCP-1 binds with human tu-mor 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,type Ⅱ cytoskeletal 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"-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 re-search may promote the development of colon cancer diagnostic technology research and provide new ideas and technical routes for tumor diagnostic technology.

Colon cancerTCP-1PeptideCytokeratin 5Pharmacokinetics/pharmacodynamics(PK/PD)

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

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State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing 100050,China

School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong,China

Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences国家自然科学基金国家自然科学基金Key Project of Beijing Natural Science FoundationNational Hightech Research and Development Plan(863 Plan)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD StudyShimadzu(China)Co.,Ltd

2021-I2M-1-027T21929728140299771810072014AA020803Z141102004414062

2024

10.1016/j.cclet.2023.108235

中国化学快报(英文版)
中国化学会

中国化学快报(英文版)

CSTPCD
影响因子：0.771
ISSN：1001-8417
年,卷(期)：2024.35(3)
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