Submission Type

Poster

Start Date

April 2020

Abstract

G-quadruplexes are non-canonical higher order DNA structures formed from guanine rich sequences, made up of stacked G-tetrads stabilized by Hoogsteen base pairing and K+ ions. G-quadruplexes are overrepresented in the promoter regions of oncogenes and the 5’UTR of mRNA1. As a result, G-Quadruplexes have been implicated as targets for possible anti-cancer therapeutic agents to treat previously “undruggable” targets like the c-myc and ras oncogenes1. The human telomeric repeat, [5’G3(T2AG3)3], is a repeating, single stranded DNA sequence that can form G-quadruplexes. Telomerase, an enzyme expressed in ~90% of all cancers, is responsible for extending telomeric repeats, making cancer cells immortal. It has been shown that stabilization of telomeric G-quadruplexes can inhibit telomerase activity and therefore block the survival of cancer cells2. The compounds used in the study are a group of abietane diterpene natural products from Hyptis verticillata, a plant native to the Caribbean and central America that has been used traditionally as an ethnomedicine that has been shown to have therapeutic effects. Some of these effects include anti-microbial, anti-inflammatory, and even anti-cancer activities3. Using several biophysical techniques, we have investigated the binding characteristics of these compounds to G-quadruplex DNA as a possible rationale for their observed anti-cancer therapeutic effects.

Comments

Faculty sponsor: Ruel McKnight

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Apr 22nd, 12:00 AM

206— Binding of Telomeric DNA G-Quadruplexes by Abietane Diterpene Natural Products

G-quadruplexes are non-canonical higher order DNA structures formed from guanine rich sequences, made up of stacked G-tetrads stabilized by Hoogsteen base pairing and K+ ions. G-quadruplexes are overrepresented in the promoter regions of oncogenes and the 5’UTR of mRNA1. As a result, G-Quadruplexes have been implicated as targets for possible anti-cancer therapeutic agents to treat previously “undruggable” targets like the c-myc and ras oncogenes1. The human telomeric repeat, [5’G3(T2AG3)3], is a repeating, single stranded DNA sequence that can form G-quadruplexes. Telomerase, an enzyme expressed in ~90% of all cancers, is responsible for extending telomeric repeats, making cancer cells immortal. It has been shown that stabilization of telomeric G-quadruplexes can inhibit telomerase activity and therefore block the survival of cancer cells2. The compounds used in the study are a group of abietane diterpene natural products from Hyptis verticillata, a plant native to the Caribbean and central America that has been used traditionally as an ethnomedicine that has been shown to have therapeutic effects. Some of these effects include anti-microbial, anti-inflammatory, and even anti-cancer activities3. Using several biophysical techniques, we have investigated the binding characteristics of these compounds to G-quadruplex DNA as a possible rationale for their observed anti-cancer therapeutic effects.

 

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