Medicinal Chemistry

Faculty

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Fast, Walter L., Ph.D.
Wm. I. Dismukes Fellowship in Pharmacy
Associate Professor of Med. Chem.
BME 6.202D
512-232-4000
walt.fast@austin.utexas.edu


Research Interests

Our research focuses on the mechanism and inhibition of various enzyme systems, including:

  1. The pentein superfamily, which includes dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that regulates nitric oxide production, and is a putative drug target to treat septic shock, idiopathic pulmonary fibrosis, melanoma, and other conditions marked by nitric oxide overproduction. We use a combination of techniques to define the chemical and kinetic mechanism of this enzyme and to develop small molecule modulators of its activity as biochemical tools and as lead compounds for therapeutic development. We recently discovered that halopyridines can serve as covalent modifiers of this enzyme, and are studying their wider application in chemical biology and medicinal chemistry.

  2. Metal-dependent beta-lactamases, including the global superbug threat: New Delhi metallo-beta-lactamase (NDM). We are investigating the mechanism and specificity of this enzyme and use rational, virtual, fragment-based and more traditional screening methods for the development of inhibitors to counteract this antibiotic resistance determinant. More generally, we use this system to develop methods to design covalent inhibitors for enzymes with non-covalent mechanisms.

  3. Quorum-quenching enzymes capable of degrading the small molecules that many bacteria use to coordinate gene expression across a population. Specifically, we are studying the N-acyl-homoserine lactone (AHL) lactonases in the metallo-beta-lactamase superfamily, and the AHL acylases in the N-terminal nucleophile family of enzymes. We are working to understand and manipulate the determinants of ligand recognition and catalysis and to determine how these enzymes impact the behavior and composition of mixed microbial cultures.

Recent Articles
  • Characterization of purified New Delhi metallo-beta-lactamase-1 (2011) Biochemistry 50, 10102-10113

  • Discovery of halopyridines as quiescent affinity labels: inactivation of dimethylarginine dimethylaminohydrolase (2011) J. Am. Chem. Soc. 133, 1553-1562.

  • Rational design of a transition state analogue with picomolar affinity for Pseudomonas aeruginosa PvdQ, a siderophore biosynthetic enzyme (2013) ACS Chem Biol 8. 2192-2200.

  • Developing an irreversible inhibitor of human DDAH-1, an enzyme upregulated in melanoma. (2014) ChemMedChem 9, 792-797


More information about Dr. Fast
> Fast Lab Personal Pages
Last Reviewed: June 10, 2014

Division Information

Mailing Address:
The University of Texas
at Austin
Medicinal Chemistry
BME 6.202
College of Pharmacy
The University of Texas
at Austin
2409 University Ave.
Stop A1900
Austin, TX, USA
78712-1113

Email Address: pharmacy
@austin.utexas.edu

Phone: 512-471-5263
Fax: 512-232-2606


Davis Among Provost's Teaching Fellows

Davis
Dr. Patrick Davis is among 20 leading faculty innovators who have been appointed as inaugural Provost's Teaching Fellows.
>Read more about this award.

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