Dissertation > Excellent graduate degree dissertation topics show

Selection and Molecular Simulation of Lead Peptides Dual-Targeting MMP14 and Metal Ions

Author: LiangZhiJuan
Tutor: ZuoZhiJuan
School: Southwest Jiaotong University
Course: Biochemistry and Molecular Biology
Keywords: MMP14 phage random peptide library subtraction cell surface biopanning consensus sequence molecular simulation
CLC: R730.2
Type: Master's thesis
Year: 2011
Downloads: 53
Quote: 0
Read: Download Dissertation

Abstract


Cancer is a kind of disease which is seriously harmful for people’s life and health. Scientists all over the world are trying their best to seek and find the methods and medicine for early diagnosis and efficiently treatment of cancers. Among all the tumor associated target proteins, MMPs play a key role in tumor metagensis and development.MMP14 as the firstly identified membrane-type matrix metalloproteinase can directly and indirectly degrade ECM and regulate adhesion molecules,MMP14 was considered to be most closely to tumor invasion.In this study, we utilized the MMP14 induced expressed human osteogenic sarcoma cell MG-63 cells as the target for the subtraction cell surface biopanning of small binding peptides from phage display peptides library. Phages were enriched and targeting sequences were obtained. In addition, mulitiple sequences alignment as well molecular simulations and in vitro assay were used in the hope of finding lead binding peptides dual targeting MMP14 and metal ions.The results showed that phages were abundantly enriched after 4-5 rounds of biopanning and we obtained totally 8 different peptide sequences. All sequences were searched by Genbank and had no homology to the database, so all sequences were discovered firstly. Combined to the previous selected sequences, a panel of possible peptide consensus sequences were found as:AHQ/SLH/P, HHXH, L/I/EPLL/I, MKPSR/ MPKSR,K/RAPK/TS, ARXQ. Molecular simulation and docking further confirmed that the consensus sequences can dock well to the catalytic domains of MMP14 at the sites of amino acids 120-125 and are relatively specific for MMP14, but it can not dock well to the HX domain of MMP14. Due to the docking sites is at the Zn ion binding sites,so we concluded that some of the phage peptides were not only targeted to MMP14 but also had affinities for Ni2+ and Zn2+ ions, subsequent determination of metal ion affinity experiments also support this conclusion. Cell biological study showed that several assayed monoclonal MMP14 phages containing binding peptides could well inhibit the viability of MG-63 cells.In vitro study showed that the selected consensus peptides had potential in inhibiting MG-63 cells viability atμg levels, it showed a obviously dose-dependent and at the concentration of 10μg /ml the inhibition rate of AHQLH can reach 41.6%. Compared to the original antimicrobial peptides, the new designed fusion peptide can better inhibit the viability of MG-63 cells. To further confirm that the consensus sequences can well targeted at MMP14, we selected HEPG-2 cells which can express MMP14 protein and Hela and MCF-7 cells which can not express to do MTT determination, the results showed that all synthesized peptides can inhibit viability of HEPG-2 cells at some extent however had little effect on Hela and MCF-7 cells further confirming that the consensus sequences were targeted at the MMP14 protein to inhibit cell viability, the follow-up studies of mechanism are still in progress.The consensus sequences were novel and relatively specific to MMP14 may be used as lead peptides for MMP14 based tumor study and therapeutic drug development.

Related Dissertations

  1. Study of Interaction between Epoxy Molecules and Carbon Fiber Surface with Molecular Simulation,TB332
  2. 1. Improvement of tmTNF-α in Insulin Resistance of Adipocytes and Its Underlying Mechanism. 2. Construction of Conserved Sequence Deleted TNF-α Mutant and the Trimerization of Remodeled TNFRBP.,R587.1
  3. Research on Extraction Mechanism and Process of Lithium from Salt Lake Brine,TS396.1
  4. Preparation and Computer Simulation of Polylactide/Organomontmorillonite Nanocomposites,TB383.1
  5. Molecular Simulation Study of Gases Adsorption and Separation in Metal-Organic Frameworks,TQ028.15
  6. Peptide targeting human FoxMlc lead drug screening and molecular modeling,R730.2
  7. Study of Adsorption and Phase Behavior of Fuild in Different of Confinement Space and CMK Materials,O561.4
  8. Molecular Dynamics Simulations of Cellulose/SiO2 Nanocomposites,TB383.1
  9. Molecalar Simulation on Interface of CF/PPEK/TI Fiber Metal Laminates,TB333
  10. Molecular Simulation Study of Betaine Zwitterionic Self-assembled Monolayers on Au(111),Q503
  11. To Initially Explorate the Relationship Between the EB Virus and Cytomegalo Virus Infection and Type 1 Autoimmune Hepatitis,R575.1
  12. Molecular Simulation of the Interaction between Hami Inertinite Structure and Gases of CH4, CO2 and H2O,O647.31
  13. The Theoretical Research of Hydrogen Storage Capacities of Ion-Exchanged Zeolites Mazzite and Levyne,TK91
  14. Whole-cell Subtractive Screening the Peptides Binding T Lymphocytes with the Phage Peptide Library of Mycobacterium Tuberculosis,R378
  15. Studies on the Problem of Phase Separation of Ethanol Gasoline,TE626.21
  16. Molecular Simulation and Experimental Study on Propylene Dehumidification Through PVA-PAA Blend Membrane,TQ028.8
  17. Studies on the Acid Degradation Process of Total Ginsenosides in the Roots of Panax Ginseng C. A.Mey. and Glycosylation of Novel Panaxadiol,R285.5
  18. Screening and Identification of the Peptides Specifically Binding to Lung Cancer by Using Phage Display in Vivo,R734.2
  19. Condensation of Amino Acids on Hydroxyapatite,O621.13
  20. Study on the Inhibitory Action of Peptides Bound to Human Prostate Carcinoma Cells in the Metastasis of Prostatic Cancer,R737.25
  21. Molecular Simulation of Adsorption and Diffusion of Methane in Deformed Coal,P618.11

CLC: > Medicine, health > Oncology > General issues > Tumor pathology, etiology
© 2012 www.DissertationTopic.Net  Mobile