Submission Type
Poster
Start Date
4-26-2023
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 telomeric and c-myc G4 sequences were investigated, with an emphasis on c-myc G4. This was done by probing the G4 structures with a variety of known and novel compounds such as quinacrine, TMPyP4 and NDI derivatives. Using the biophysical techniques of isothermal titration calorimetry (ITC), fluorescent displacement, thermal melting, and circular dichroism (CD) spectroscopy, the binding characteristics of these compounds to G4 DNA were investigated.
Recommended Citation
Michaels, Alexander; Haidari, Sameela; and Fetzer, Courtney, "195 - Targeting Telomeric and c-MYC G4 DNA as an Anticancer Approach" (2023). GREAT Day Posters. 32.
https://knightscholar.geneseo.edu/great-day-symposium/great-day-2023/posters-2023/32
Included in
195 - 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 telomeric and c-myc G4 sequences were investigated, with an emphasis on c-myc G4. This was done by probing the G4 structures with a variety of known and novel compounds such as quinacrine, TMPyP4 and NDI derivatives. Using the biophysical techniques of isothermal titration calorimetry (ITC), fluorescent displacement, thermal melting, and circular dichroism (CD) spectroscopy, the binding characteristics of these compounds to G4 DNA were investigated.
Comments
Sponsored by Ruel McKnight