Drug Discovery on Guanylate Monophosphate Kinase Through a Combined in Vitro and Nmr Screening
Faculty Mentor
Mark Vincent Dela Cerna
Location
Savannah Ballroom
Type of Research
On-going
Session Format
Poster Presentation
College
College of Science & Mathematics
Department
Department of Chemistry and Biochemistry
Abstract
Guanylate monophosphate kinase (GMPK) plays a critical role in nucleotide synthesis and is involved in both de novo and salvage pathways of the synthesis of GTP. It catalyzes the ATP-dependent phosphorylation of GMP to form GDP. As it is the only enzyme that catalyzes this reaction in human cells, it is an essential enzyme for nucleic acid synthesis. There is evidence that knockdown of GMPK leads to selective killing of select lung cancer cell lines with minimal effect on normal cells during the treatment time. This indicates that GMPK may have potential therapeutic implications as a drug target. To this end, we are screening molecules for potential GMPK therapeutics using an NADH-coupled assay. We are optimizing the assay in a 96-well format for high-throughput screening of compound libraries. At the same time, we are screening a fluorinated fragment library using 19F-NMR to identify molecules that bind to GMPK which will then be evaluated for their ability to inhibit GMPK enzymatic activity. We have identified several promising fragments. Future directions include structure-activity relationship studies, characterization of interaction and inhibition mechanisms, and evaluation of inhibitory effects on the growth of lung cancer cell lines.
Program Description
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Start Date
4-21-2026 10:00 AM
End Date
4-21-2026 12:00 PM
Recommended Citation
Patel, Chahat and Winkler-Durst, Kaelin, "Drug Discovery on Guanylate Monophosphate Kinase Through a Combined in Vitro and Nmr Screening" (2026). GS4 Student Scholars Symposium. 42.
https://digitalcommons.georgiasouthern.edu/research_symposium/2026A/2026A/42
Drug Discovery on Guanylate Monophosphate Kinase Through a Combined in Vitro and Nmr Screening
Savannah Ballroom
Guanylate monophosphate kinase (GMPK) plays a critical role in nucleotide synthesis and is involved in both de novo and salvage pathways of the synthesis of GTP. It catalyzes the ATP-dependent phosphorylation of GMP to form GDP. As it is the only enzyme that catalyzes this reaction in human cells, it is an essential enzyme for nucleic acid synthesis. There is evidence that knockdown of GMPK leads to selective killing of select lung cancer cell lines with minimal effect on normal cells during the treatment time. This indicates that GMPK may have potential therapeutic implications as a drug target. To this end, we are screening molecules for potential GMPK therapeutics using an NADH-coupled assay. We are optimizing the assay in a 96-well format for high-throughput screening of compound libraries. At the same time, we are screening a fluorinated fragment library using 19F-NMR to identify molecules that bind to GMPK which will then be evaluated for their ability to inhibit GMPK enzymatic activity. We have identified several promising fragments. Future directions include structure-activity relationship studies, characterization of interaction and inhibition mechanisms, and evaluation of inhibitory effects on the growth of lung cancer cell lines.
