BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16)
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2016
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ndltd-OhioLink-oai-etd.ohiolink.edu-miami14697204592021-08-03T06:37:49Z BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) Meng, Fan 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. 2016-07-29 English text Miami University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=miami1469720459 http://rave.ohiolink.edu/etdc/view?acc_num=miami1469720459 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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English |
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Biochemistry |
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Biochemistry Meng, Fan BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) |
author |
Meng, Fan |
author_facet |
Meng, Fan |
author_sort |
Meng, Fan |
title |
BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) |
title_short |
BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) |
title_full |
BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) |
title_fullStr |
BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) |
title_full_unstemmed |
BIOCHEMICAL CHARACTERIZATION AND ZINC BINDING GROUP (ZBGS) INHIBITION STUDIES ON THE CATALYTIC DOMAINS OF MMP7 (CDMMP7) AND MMP16 (CDMMP16) |
title_sort |
biochemical characterization and zinc binding group (zbgs) inhibition studies on the catalytic domains of mmp7 (cdmmp7) and mmp16 (cdmmp16) |
publisher |
Miami University / OhioLINK |
publishDate |
2016 |
url |
http://rave.ohiolink.edu/etdc/view?acc_num=miami1469720459 |
work_keys_str_mv |
AT mengfan biochemicalcharacterizationandzincbindinggroupzbgsinhibitionstudiesonthecatalyticdomainsofmmp7cdmmp7andmmp16cdmmp16 |
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1719440426895671296 |