Type
Text
Type
Thesis
Advisor
Rizzo, Robert C | Sampson, Nicole S | Boon, Elizabeth.
Date
2012-08-01
Keywords
anticancer drug, docking, MMP-9 | Chemistry--Biochemistry
Department
Department of Chemistry
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/71320
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Matrix metalloproteinases (MMPs) play an important role in cancer progression by degrading extracellular matrix components, promoting tumor cell migration, and thus enhancing tumor metastasis. Several generations of anticancer drug were designed to inhibit the proteolytic functions of MMPs, but these drugs failed in clinic trails due to lack of selectivity. This study focused on the hemopexin domain of MMP-9, a nonproteolytic domain, which is essential for MMP-9 regulated tumor cell migration. Compared with the catalytic domain of MMPs, fewer amino acids are conserved between the hemopexin domains of MMP family members. This difference provides the principle basis for identification of inhibitors targeting the hemopexin domain with high selectivity and specificity. An in silico docking approach was employed to screen for novel small-molecule compound that bind to the hemopexin domain of MMP-9. Seven computational hits were evaluated in biochemical binding assays. Of these, 4 compounds were identified that have micromolar affinities for the hemopexin domain of MMP-9,74 pages
Recommended Citation
Li, Zhu, "Identification of small molecules that bind to the hemopexin domain of matrix metalloproteinase-9" (2012). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 526.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/526