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Importance of Chiral Recognition in Designing Metal-Free Ligands for G-Quadruplex DNA.

ABSTRACT: Four pairs of amino acid-functionalized naphthalenediimide enantiomers (d- and l-lysine derived NDIs) were screened toward G-quadruplex forming sequences in telomeres (h-TELO) and oncogene promoters: c-KIT1, c-KIT2, k-RAS and BCL-2. This is the first study to address the effect of point chirality toward G-quadruplex DNA stabilization using purely small organic molecules. Enantioselective behavior toward the majority of ligands was observed, particularly in the case of parallel conformations of c-KIT2 and k-RAS. Additionally, Nε-Boc-l-Lys-NDI and Nε-Boc-d-Lys-NDI discriminate between quadruplexes with parallel and hybrid topologies, which has not previously been observed with enantiomeric ligands.

SUBMITTER: Rasadean DM

PROVIDER: S-EPMC6514905 | biostudies-other | 2019 Apr

REPOSITORIES: biostudies-other

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Importance of Chiral Recognition in Designing Metal-Free Ligands for G-Quadruplex DNA.

Răsădean Dora M DM Harrison Samuel W O SWO Owens Isobel R IR Miramont Aucéanne A Bromley Frances M FM Pantoș G Dan GD

Molecules (Basel, Switzerland) 20190415 8

Four pairs of amino acid-functionalized naphthalenediimide enantiomers (d- and l-lysine derived NDIs) were screened toward G-quadruplex forming sequences in telomeres (h-TELO) and oncogene promoters: c-KIT1, c-KIT2, k-RAS and BCL-2. This is the first study to address the effect of point chirality toward G-quadruplex DNA stabilization using purely small organic molecules. Enantioselective behavior toward the majority of ligands was observed, particularly in the case of parallel conformations of c ...[more]

PMID: 30991655

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