Submission Type

Poster

Start Date

4-21-2022

Abstract

G-quadruplex (G4) DNA are non-canonical higher order DNA structures formed from guanine rich sequences, made up of stacked G-tetrads stabilized by non-Watson-Crick (Hoogsteen) base pairing and K+ ions. Early interests in G4 DNA were spurred on by the revelation that G4 was formed in telomeric DNA sequences at the end of our chromosomes. This was particularly promising given that G4 structures formed in telomeric DNA were also found to inhibit an enzyme known as telomerase, which is overexpressed (>90%) in cancer cells. Cancer cells require telomerase activity for survival and “immortality”, therefore stabilization of telomeric G4 can inhibit telomerase activity and prevent the survival of cancer cells. More recently, G4 DNA has also been shown to be overrepresented in the promoter regions of oncogenes (e.g., c-myc and ras genes) and the 5’UTR of mRNA. As a result, G4 DNA represents a viable target for possible anti-cancer therapeutic agents to treat previously “undruggable” sites such as the c-myc and ras oncogenes. In this work, G4 structures formed at both human telomeric and c-myc sequences will be investigated by targeting/probing them using a variety of known and novel compounds. Using biophysical techniques such as fluorescent displacements assays, thermomelting, and circular dichroism (CD) spectroscopy, the binding characteristics of these compounds to G4 DNA will be investigated for their efficacy as a possible anti-cancer therapeutic strategy.

Comments

Sponsored by Ruel McKnight

Share

COinS
 
Apr 21st, 12:00 AM

100 -- Targeting Telomeric and c-MYC G4 DNA as an Anticancer Approach

G-quadruplex (G4) DNA are non-canonical higher order DNA structures formed from guanine rich sequences, made up of stacked G-tetrads stabilized by non-Watson-Crick (Hoogsteen) base pairing and K+ ions. Early interests in G4 DNA were spurred on by the revelation that G4 was formed in telomeric DNA sequences at the end of our chromosomes. This was particularly promising given that G4 structures formed in telomeric DNA were also found to inhibit an enzyme known as telomerase, which is overexpressed (>90%) in cancer cells. Cancer cells require telomerase activity for survival and “immortality”, therefore stabilization of telomeric G4 can inhibit telomerase activity and prevent the survival of cancer cells. More recently, G4 DNA has also been shown to be overrepresented in the promoter regions of oncogenes (e.g., c-myc and ras genes) and the 5’UTR of mRNA. As a result, G4 DNA represents a viable target for possible anti-cancer therapeutic agents to treat previously “undruggable” sites such as the c-myc and ras oncogenes. In this work, G4 structures formed at both human telomeric and c-myc sequences will be investigated by targeting/probing them using a variety of known and novel compounds. Using biophysical techniques such as fluorescent displacements assays, thermomelting, and circular dichroism (CD) spectroscopy, the binding characteristics of these compounds to G4 DNA will be investigated for their efficacy as a possible anti-cancer therapeutic strategy.

 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.