Non-canonical DNA structures, notably G-quadruplexes and i-motifs, are gaining popularity because biological evidence suggests that they play crucial roles in a variety of disease-related biological processes. G-quadruplex DNA structures are composed of planar guanine tetrads which are engaged in effective p-p stacking and are further stabilized by monovalent central cation (e.g. K+ or Na+), Figure 1A. Sequences with G-quadruplex forming potential are present in telomeres and in oncogene promoters, according to bioinformatics studies. I-motifs are intercalated hemi-protonated cytosine-rich structures formed in the C-rich regions of genome complementary to those with high G-quadruplex forming potential. I will present our structural and biophysical characterization of human telomeric DNA (Tel22), telomeric DNA from Tetrahymena thermofila (THM) as well as a G-rich DNA from a variety of oncogene promoters alone and in complex porphyrin ligands. Due to the excellent optical properties of porphyrins, we investigate their binding to G-quadruplex DNA using UV-vis, circular dichroism, and fluorescence titrations. We obtain thermodynamic parameters of binding via ITC titrations. We crystallized NMM in complex with Tel22 (Figure 1B, C) and THM. I will discuss the details of the structures. Finally, I will share our preliminary data on the structure of an i-motif from the HRAS oncogene as well as repetitive DNA implicated in replication stress. Our findings are of great importance for the development of new and efficient anticancer therapies. Figure 1. G-quadruplex DNA and its complex with N-methylmesoporphyrin IX, NMM. (A) The structure of G-tetrad. (B) Crystals of NMM in complex with Tel22. (C) Electron density and the model for Tel22-NMM complex.

Non-canonical DNA structures and their interactions with small molecule ligands

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.