Horn, James R.||Hagen, Timothy J.
M.S. (Master of Science)
Department of Chemistry and Biochemistry
Antibacterial agents; Drug resistance in microorganisms; Methionine; Aminopeptidases
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.
Chen, Congling, "Methionine aminopeptidase as a target for the discovery of novel antibacterial agents" (2016). Graduate Research Theses & Dissertations. 3954.
vii, 144 pages
Northern Illinois University
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