Development of microfluidic platforms for the synthesis of metal complexes and evaluation of their DNA affinity using online FRET melting assays

Chemical Science
Viktoria RakersRamon Vilar

Abstract

Guanine-rich DNA sequences can fold into quadruple-stranded structures known as G-quadruplexes. These structures have been proposed to play important biological roles and have been identified as potential drug targets. As a result, there is increasing interest in developing small molecules that can bind to G-quadruplexes. So far, these efforts have been mostly limited to conventional batch synthesis. Furthermore, no quick on-line method to assess new G-quadruplex binders has been developed. Herein, we report on two new microfluidic platforms to: (a) readily prepare G-quadruplex binders (based on metal complexes) in flow, quantitatively and without the need for purification before testing; (b) a microfluidic platform (based on FRET melting assays of DNA) that enables the real-time and on-line assessment of G-quadruplex binders in continuous flow.

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Citations

Jun 14, 2018·Chemistry : a European Journal·Anna ŁęczkowskaRamon Vilar
Sep 13, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Kimberley J DavisStephen F Ralph
May 7, 2019·Chemical Reviews·Audrey BeillardFrédéric Lamaty
Jul 10, 2019·Journal of the American Chemical Society·Jinbo ZhuUlrich F Keyser

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Methods Mentioned

BETA
ChIP
FRET
NMR
1
fluorescence resonance
PCR

Software Mentioned

AutoCad Inventor
LabView
OriginPro
Matlab

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