Event Title
Mechanism of Telomerase Inhibition by Novel Non-Nucleosidic Drug Candidates
Presentation Type
Poster/Portfolio
Presenter Major(s)
Biomedical Sciences, Cell and Molecular Biology
Mentor Information
William Schroeder, Robert Smart, Suganthi Sridhar, Agnieszka Szarecka
Department
Chemistry, Biomedical Sciences, Cell and Molecular Biology
Location
Henry Hall Atrium 7
Start Date
10-4-2013 11:00 AM
End Date
10-4-2013 12:00 PM
Keywords
Life Science
Abstract
Telomerase is a reverse transcriptase enzyme that adds telomeric DNA repeats to the ends of linear chromosomes. In normal somatic cells telomerase activity is very low, which causes the cells to have limited capacity for proliferation. However, many types of cancer cells have the ability to overexpress telomerase enabling them to divide so aggressively. Thus telomerase is an important anti-cancer drug target and designing an effective inhibitor will potentially aid cancer therapy in all telomerase-expressing tumors. Here we present the results of computational modeling of interactions between telomerase TERT domain and several inhibitory drug candidates. On the basis of our protein-ligand docking simulations, domain flexibility and bioinformatics analysis, we propose three different modes of drug binding to telomerase leading to the inhibition of its TERT domain function via distinct mechanisms. Our project will aid and inform further efforts in inhibitor design and optimization.
Mechanism of Telomerase Inhibition by Novel Non-Nucleosidic Drug Candidates
Henry Hall Atrium 7
Telomerase is a reverse transcriptase enzyme that adds telomeric DNA repeats to the ends of linear chromosomes. In normal somatic cells telomerase activity is very low, which causes the cells to have limited capacity for proliferation. However, many types of cancer cells have the ability to overexpress telomerase enabling them to divide so aggressively. Thus telomerase is an important anti-cancer drug target and designing an effective inhibitor will potentially aid cancer therapy in all telomerase-expressing tumors. Here we present the results of computational modeling of interactions between telomerase TERT domain and several inhibitory drug candidates. On the basis of our protein-ligand docking simulations, domain flexibility and bioinformatics analysis, we propose three different modes of drug binding to telomerase leading to the inhibition of its TERT domain function via distinct mechanisms. Our project will aid and inform further efforts in inhibitor design and optimization.