Computational And Experimental Research On HCPT Binding Peptide

To search for homologous sequence mode of 10-Hydroxyl camptothecine(HCPT) binding peptides and their binding mechanisim as well as HCPT binding proteins by researching HCPT binding peptides, so as to offer help with researches on decoding the anticancer mechanism of HCPT, the mechanism underlying resistance to HCPT and the mechanism of its side effects.Biotin-HCPT compound was synthesized with the esterification-dehydration method, purified with Resourse15 reversed-phase column and analyzed with LC-MS. The anticancer activity of Biotin-HCPT was identified by SRB method. On the basis of Biotin-HCPT-avidin- magnetic beads, fourteen HCPT binding peptides were identified by phage display. The homologous sequence mode of HCPT binding peptides was identified as xxxxxLxPxxxx while the homologous sequence mode of degeneracy HCPT binding peptides was identified as xGxxGGGNxGGx by sequence alignment analysis. A series of HCPT binding proteins related to tumor was captured by bioinformatical analysis, which mainly include oncoproteins, oncoproteins targeted proteins, oncogene regulators, tumor specific antigens, transmembrane receptors and receptor interacting proteins, transcription factors, two protein tyrosine phosphatases of receptor type, one G protein-coupled receptor, one phosphatidylinosito l-3-phosphate-5-kinase, one signal-induced proliferation-associated protein and several resistant proteins.Structure model of HCPT was built and optimized. Structure models of HCPT binding peptides were built and then optimized by molecular dynamics. The binding effects between HCPT and HCPT binding peptides were verificated and analyzed by docking.