Date of Last Revision
2023-05-02 21:28:13
Major
Chemistry - Biochemistry
Degree Name
Bachelor of Science
Date of Expected Graduation
Spring 2017
Abstract
Fragment-based drug design (FBDD) is a method of pharmaceutical research involving characterization of small “fragment” molecule interactions with a target protein. These fragments are optimized with the addition of a nucleophilic “warhead” moiety. Several novel fragment-warhead adducts have been synthesized in house by group member Ram Khattri Ph.D. The experiment investigates reactivity of these adducts with glutaredoxin protein (Grx) orthologs from Homo sapiens, Pseudomonas aeruginosa and Brucella melitensis. Three novel fragment-warhead adducts have been identified to cause weakly bacteriostatic and bacteriocidal effects, most with minimum inhibitory concentration values near 1.28 mg/mL. Discussed herein are molecular effects of these fragment-warhead compounds on Grx, such as their association in inducing Grx oligomerization. Further investigation of the fragment-warhead adduct coumarin acrylamide was performed due to its fluorescent properties. Use of Grx as a druggable candidate for development of a putative antibiotic has been a relatively untapped target until recently. These results may help further characterize Grx, and its ability to mediate bacterial survivability, to aid in the fight against multi-drug resistant and opportunistic bacterial infections such as pneumonia and brucellosis.
Research Sponsor
Dr. Thomas Leeper
First Reader
Dr. Wiley Youngs
Second Reader
Dr. Claire Tessier
Recommended Citation
Caras, Andrew J., "Effects of novel fragment-warhead adducts in situ and in vitro with glutaredoxin orthologs." (2017). Williams Honors College, Honors Research Projects. 403.
https://ideaexchange.uakron.edu/honors_research_projects/403