title: Detection of Tumor Invasive Biomarker using a Peptamer of Signal Conversion and Signal Amplification.
abstract: Inspired by the structural and functional features of proteins in cell signaling, a switchable peptide is designed in this work. This switchable peptide is named a "peptamer," and it can react to ligand binding with conformational change and activation/deactivation of catalytic ability. The peptamer is constructed by elaborately integrating several different peptide motifs with targeting and catalytic abilities. Thus, targeted binding of the peptamer to an integrin can be regulated by a synthetic ligand. Moreover, the conformational rearrangement of the peptamer induced by both integrin and the synthetic ligand can resolve in altered affinity of the peptamer for a catalytic cofactor, cupric ion. This leads to greatly contrasted efficiency of catalysis in the presence/absence of integrin. This distinct switching on/off of catalytic activity also enables a bioassay of tissue integrin expression in clinical samples of thyroid carcinoma. Experimental results reveal that the detected integrin level parallels the state of lymph node metastasis. Therefore, this simple peptide model may help to understand the structural reconfiguration of proteins involved in cellular signal transduction, as well as to provide a new means to assess protein activity under pathological conditions such as cancer.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, Department of Biochemistry, Nanjing University , Nanjing 210093, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, Department of Biochemistry, Nanjing University , Nanjing 210093, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University , Nanjing 210011, China.
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University , Nanjing 210011, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, Department of Biochemistry, Nanjing University , Nanjing 210093, China.|Laboratory of Biosensing Technology, School of Life Sciences, Shanghai University , Shanghai 200444, China.
authors.forename: Genxi
authors.initials: G
authors.lastname: Li
authors.affiliation: Laboratoire de la Barrière Hémato-encéphalique, Faculté des Sciences, Université d'Artois , rue Souvraz SP18, 62307 CEDEX Lens, France.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Karamanos
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000737:chemistry; D002384:Catalysis; D002413:Cations, Divalent; D003300:Copper / Q000737:chemistry; D055664:Electrochemical Techniques; D006801:Humans; D016023:Integrins / Q000032:analysis* / Q000737:chemistry; D008024:Ligands; D008207:Lymphatic Metastasis; D047028:Macrocyclic Compounds / Q000737:chemistry; D009361:Neoplasm Invasiveness; D010455:Peptides / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000473:pathology; D000099246:Cucurbit(n)urils
chemical_list: D014408:Biomarkers, Tumor; D002413:Cations, Divalent; D003300:Copper; D016023:Integrins; D008024:Ligands; D047028:Macrocyclic Compounds; D010455:Peptides; D000099246:Cucurbit(n)urils