Author Type

Graduate Student

Date of Award

2007

Document Type

Dissertation

Publication Status

Version of Record

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Brew, Keith

Abstract

Alterations in activities of one family of proteases, the metzincins have been implicated in an array of physiological and pathological processes. In the present study, metzincin inhibitors were developed by utilizing topologically constrained peptides and pseudopeptides. The endothelin-family framework was used to develop a disulfideconstrained topology. This framework was chosen due to its three-dimensional similarity with a family of endogenous metzincin inhibitors, the tissue inhibitors of metalloproteases (TIMPs). The collagenous triple-helix was chosen as a second framework, because only a subset of proteolytic enzymes have the capacity to bind and hydrolyze a triple-helix. Both templates were successfully modified to generate an array of inhibitors. These inhibitors displayed subnanomolar to micromolar apparent Ki values, while being moderately selective metzincin inhibitors. In both cases the threedimensional structure was determined to be important for activity. This work encourages the further development of both frameworks as metzincin inhibitors.

Extent

175 p.

Comments

Includes bibliography.|Dissertation (Ph.D.)--Florida Atlantic University, 2007.|FAU Electronic Theses and Dissertations Collection|Charles E. Schmidt College of Medicine|Includes bibliography.

Identifier

FA00000867

Format

pdf

Download

Share

COinS