Document Type
Thesis - University Access Only
Award Date
1998
Degree Name
Master of Science (MS)
Department / School
Pharmaceutical Sciences
Abstract
Collagenase IV, a matrix metalloproteinase (MMP-2), the enzyme utilized by metastatic tumor cells to hydrolyze collagen IV which is the major physical barrier to the movement of malignant tumor cells across the basement membrane, has been proposed as a target for the development of antimetastatic agents. The purpose of this research was to design and synthesize collagenase IV inhibitors. Synthetic peptide substrates were used as models for the design of inhibitors. To produce inhibitors from these substrates the scissile amide bond contained within the Gly-X dipeptide of the substrates was replaced by a non-hydrolyzable phosphonamide. The synthesis of target compounds followed a sequence of protection and deprotection. Condensation of the phosphoryl chloride with appropriately protected amino acids yielded the corresponding dipeptides. Three phosphonamidate dipeptide analogues were prepared. One of the compounds showed some inhibition of Collagenase IV at 10 mM. The other two were inactive.
Library of Congress Subject Headings
Collagenases -- Inhibitors
Peptides
Metastasis
Format
application/pdf
Number of Pages
56
Publisher
South Dakota State University
Recommended Citation
Fan, Yi, "Phosphonamidate Peptide Analogues as Inhibitors of Collagenase IV : Potential Antimetastatic Drugs" (1998). Electronic Theses and Dissertations. 1317.
https://openprairie.sdstate.edu/etd2/1317