Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


toledo1352438577.pdf (2.15 MB)

ETD Abstract Container

Abstract Header

Synthesis of Bisubstrate Analog Inhibitors against Aspartate Semialdehyde Dehydrogenase

Muvvala, Harinath G.
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1352438577

Abstract Details

2012, Master of Science, University of Toledo, Chemistry.
Aspartate semialdehyde dehydrogenase (ASADH) is an essential enzyme found in bacteria, fungi and plants. This enzyme is responsible for the production of several essential amino acids, and its absence in humans makes ASADH an attractive target for the development of antibiotics. The goal of the project is to design, synthesize and build species-selectivity into bisubstrate analogue inhibitors against ASADH. Analogues were choosen to synthesize based on the docking model predictions for binding affinities and selectivities against ASADHs that have been purified and characterized from different microbial species. The synthetic approach involves the parallel synthesis of secondary amine derivatives and phenyl alkyl halides. The two synthons are being coupled through nucleophilic substitution followed by hydrolysis to form the desired bisubstrate analogues. Four compounds were identified based on docking score and selectivity analyses. These analogs were synthesized and tested against ASADH. These studies have led to identification of sub-millimolar inhibitors of ASADH.This work is supported by a grant from the NIH (AI077720).
Ronald E. Viola, PhD (Advisor)
Max O. Funk, PhD (Committee Member)
Steven J. Sucheck, PhD (Committee Member)
95 p.
Biochemistry

Recommended Citations

Citations

  • Muvvala, H. G. (2012). Synthesis of Bisubstrate Analog Inhibitors against Aspartate Semialdehyde Dehydrogenase [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1352438577

    APA Style (7th edition)

  • Muvvala, Harinath. Synthesis of Bisubstrate Analog Inhibitors against Aspartate Semialdehyde Dehydrogenase. 2012. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1352438577.

    MLA Style (8th edition)

  • Muvvala, Harinath. "Synthesis of Bisubstrate Analog Inhibitors against Aspartate Semialdehyde Dehydrogenase." Master's thesis, University of Toledo, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1352438577

    Chicago Manual of Style (17th edition)

toledo1352438577
449
© 2012, all rights reserved.
This open access ETD is published by University of Toledo and OhioLINK.