title: Enzymatically Regulated Peptide Pairing and Catalysis for the Bioanalysis of Extracellular Prometastatic Activities of Functionally Linked Enzymes.
abstract: Diseases such as cancer arise from systematical reconfiguration of interactions of exceedingly large numbers of proteins in cell signaling. The study of such complicated molecular mechanisms requires multiplexed detection of the inter-connected activities of several proteins in a disease-associated context. However, the existing methods are generally not well-equipped for this kind of application. Here a method for analyzing functionally linked protein activities is developed based on enzyme controlled pairing between complementary peptide helix strands, which simultaneously enables elaborate regulation of catalytic activity of the paired peptides. This method has been used to detect three different types of protein modification enzymes that participate in the modification of extracellular matrix and the formation of invasion front in tumour. In detecting breast cancer tissue samples using this method, up-regulated activity can be observed for two of the assessed enzymes, while the third enzyme is found to have a subtle fluctuation of activity. These results may point to the application of this method in evaluating prometastatic activities of proteins in tumour.
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: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yu
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: Tianqi
authors.initials: T
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.|Laboratory of Biosensing Technology, School of Life Sciences, Shanghai University, Shanghai 200444, China.
authors.forename: Genxi
authors.initials: G
authors.lastname: Li
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Anzai
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology* / Q000556:secondary*; D045604:Extracellular Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps
chemical_list: D010455:Peptides