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BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16)

Meng, Fan
http://rave.ohiolink.edu/etdc/view?acc_num=miami1469720459

Abstract Details

2016, Doctor of Philosophy, Miami University, Chemistry and Biochemistry.
Matrix metalloproteinase 7 (MMP7/matrilysin-1) and membrane type matrix metalloproteinase 16 (MMP16/MT3-MMP) have been implicated in the progression of pathological events, such as cancer and inflammatory diseases; therefore, these two MMPs are considered as viable drug targets. In this work, we (a) provide a review of the role(s) of MMPs in biology and of the previous efforts to target MMPs as therapeutics (Chapter 1), (b) describe our efforts at over-expression, purification, and characterization of the catalytic domains of MMP7 (cdMMP7) and MMP16 (cdMMP16) (Chapters 2 and 3), (c) present our efforts at the preparation and initial spectroscopic characterization of Co(II)-substituted analogs of cdMMP7 and cdMMP16 (Chapters 2 and 3), (d) present inhibition data on cdMMP7 and cdMMP16 using zinc binding groups (ZBG) as potential scaffolds for future inhibitors (Chapter 3), and (e) summarize our data in the context of previous results and suggest future directions (Chapter 4). The work described in this dissertation integrates biochemical (kinetic assays, inhibition studies, limited computational methods), spectroscopic (CD, UV-Vis, 1H-NMR, fluorescence, and EXAFS), and analytical (MALDI-TOF mass spectrometry, isothermal calorimetry) methods to provide a detailed structural and mechanistic view of these MMPs. This work is part of overall effort to prepare selective and specific inhibitors against the MMPs, which are expected to be drug candidates in MMP-associated diseases.
Michael Crowder (Advisor)
David Tierney (Committee Chair)
187 p.
Biochemistry

Recommended Citations

Citations

  • Meng, F. (2016). BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1469720459

    APA Style (7th edition)

  • Meng, Fan. BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) . 2016. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1469720459.

    MLA Style (8th edition)

  • Meng, Fan. "BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) ." Doctoral dissertation, Miami University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=miami1469720459

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Miami University and OhioLINK.