Congling Chen

Publication Date

2016

Document Type

Dissertation/Thesis

First Advisor

Horn, James R.||Hagen, Timothy J.

Degree Name

M.S. (Master of Science)

Legacy Department

Department of Chemistry and Biochemistry

LCSH

Antibacterial agents; Drug resistance in microorganisms; Methionine; Aminopeptidases

Abstract

The rise of antibiotic resistance has been an increasingly critical global health issue. Compounding this issue is the fact that the approval of new antibiotics has dramatically decreased over the past three decades. One validated target for the discovery of new antibacterial agents is methionine aminopeptidase (MetAp). MetAp is a metallo-protein that catalyzes the hydrolysis of the N-terminal methionine residue from nascent proteins, a key step required for certain post-translational modifications. Studies have demonstrated that knock-out mutations of the MetAp gene leads to decreased cell viability or even cell death, which strengthens MetAp as a viable target for antibiotic discovery programs. This thesis describes the evaluation of small molecule MetAp inhibitors. The first project describes the overexpression, purification, and characterization of Rickettsia prowazekii MetAp I (Rp MetAP I), and the evaluation novel small molecule inhibitors against it using an activity assay in vitro. The second project focused on the MetAP enzyme from Plasmodium falciparum (PfMetAP II). Efforts were made on the producing of active PfMetAP II by replication of constructed methods.

Comments

Advisors: James R. Horn; Timothy J. Hagen.||Committee members: Gary M. Baker.||Includes bibliographical references.||Includes illustrations.

Extent

vii, 144 pages

Language

eng

Publisher

Northern Illinois University

Rights Statement

In Copyright

Rights Statement 2

NIU theses are protected by copyright. They may be viewed from Huskie Commons for any purpose, but reproduction or distribution in any format is prohibited without the written permission of the authors.

Media Type

Text

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