Peptides Designed to Target an RNA G-Quadruplex for Regulation and Inhibition of Translation
Primary Faculty Mentor’s Name
Amanda L. Stewart
Proposal Track
Student
Session Format
Poster
Abstract
G-quadraplex structures occur in guanine rich sequences of nucleotides which fold into stable tetraplexes of planar rings. G-quadruplexes are present in regions of DNA and RNA that are essential for cancer cells to proliferate indefinitely such as in telomeric and regulatory regions of oncogenes, and because of this, G-qudraplexes have become a target of study in anticancer therapeutics. G-quadruplexes are also thought to be involved in regulation of translation when present in certain mRNA sequences. A small molecule or a peptide synthesized to specifically recognize the G-quadruplex structure could display anticancer activity or may prove to inhibit translation in the case of an RNA G-quadruplex in mRNA. To explore these possibilities, a peptide was designed to mimic the small molecule inhibitors RR82 and RR110 which were previously reported in the literature and have been demonstrated to inhibit RNA G-quadraplex translation. The binding affinity for the peptide and an RNA-containing G-quadruplex will be determined using Isothermal Titration Calorimetry (ITC). The secondary structure of the peptide will be determined using circular dichroism spectroscopy (CD). Initial data will direct the synthesis of other peptide sequences which will be synthesized including the extension of the original peptide sequence to form a longer peptide that could adopt a more stable secondary structure. Multiple peptide sequences will be synthesized and characterized, and progress toward completion of this research will be reported.
Keywords
Peptide, G-quadruple, Translation inhibition
Location
Concourse/Atrium
Presentation Year
2014
Start Date
11-15-2014 2:55 PM
End Date
11-15-2014 4:10 PM
Publication Type and Release Option
Presentation (Open Access)
Recommended Citation
Patel, Srujay K. and Stewart, Amanda L., "Peptides Designed to Target an RNA G-Quadruplex for Regulation and Inhibition of Translation" (2014). Georgia Undergraduate Research Conference (2014-2015). 96.
https://digitalcommons.georgiasouthern.edu/gurc/2014/2014/96
Peptides Designed to Target an RNA G-Quadruplex for Regulation and Inhibition of Translation
Concourse/Atrium
G-quadraplex structures occur in guanine rich sequences of nucleotides which fold into stable tetraplexes of planar rings. G-quadruplexes are present in regions of DNA and RNA that are essential for cancer cells to proliferate indefinitely such as in telomeric and regulatory regions of oncogenes, and because of this, G-qudraplexes have become a target of study in anticancer therapeutics. G-quadruplexes are also thought to be involved in regulation of translation when present in certain mRNA sequences. A small molecule or a peptide synthesized to specifically recognize the G-quadruplex structure could display anticancer activity or may prove to inhibit translation in the case of an RNA G-quadruplex in mRNA. To explore these possibilities, a peptide was designed to mimic the small molecule inhibitors RR82 and RR110 which were previously reported in the literature and have been demonstrated to inhibit RNA G-quadraplex translation. The binding affinity for the peptide and an RNA-containing G-quadruplex will be determined using Isothermal Titration Calorimetry (ITC). The secondary structure of the peptide will be determined using circular dichroism spectroscopy (CD). Initial data will direct the synthesis of other peptide sequences which will be synthesized including the extension of the original peptide sequence to form a longer peptide that could adopt a more stable secondary structure. Multiple peptide sequences will be synthesized and characterized, and progress toward completion of this research will be reported.
