Controlled Pore Glass-based oligonucleotide affinity support: towards High Throughput Screening methods for the identification of conformation-selective G-quadruplex ligands.

Controlled Pore Glass-based oligonucleotide affinity support: towards High Throughput Screening methods for the identification of conformation-selective G-quadruplex ligands.
Anal Chim Acta. 2018 Nov 07;1030:133-141
Authors: Platella C, Musumeci D, Arciello A, Doria F, Freccero M, Randazzo A, Amato J, Pagano B, Montesarchio D
Abstract
Target selectivity is one of the main challenges in the search for small molecules able to act as effective and non-toxic anticancer and/or antiviral drugs. To achieve this goal, handy, rapid and reliable High Throughput Screening methodologies are needed. We here describe a novel functionalization for the solid phase synthesis of oligonucleotides on Controlled Pore Glass, including a flexible hexaethylene glycol spacer linking the first nucleoside through the nucleobase via a covalent bond stable to the final deprotection step. This allowed us preparing fully deprotected oligonucleotides still covalently attached to their supports. In detail, on this support we performed both the on-line synthesis of different secondary structure-forming oligonucleotides and the affinity chromatography-based screenings of conformation-selective G-quadruplex ligands. By using a fluorescent core-extended naphthalene diimide with different emitting response upon binding to sequences folding into G-quadruplexes of different topologies, we have been able to discriminate not only G-quadruplex vs. duplex DNA structures, but a...

Source: Analytica Chimica Acta - July 25, 2018 Category: Chemistry Authors: Platella C, Musumeci D, Arciello A, Doria F, Freccero M, Randazzo A, Amato J, Pagano B, Montesarchio D Tags: Anal Chim Acta Source Type: research