Anti-HIV activity of new higher order G-quadruplex aptamers obtained from tetra-end-linked oligonucleotides. Issue 13 (15th March 2018)

• Record Type: Journal Article
• Authors: Nici, F.; Oliviero, G.; Falanga, A. P.; D'Errico, S.; Marzano, M.; Musumeci, D.; Montesarchio, D.; Noppen, S.; Pannecouque, C.; Piccialli, G.; Borbone, N.
• Is Part Of: Organic & biomolecular chemistry. Volume 16:Issue 13(2018)
• Page Start: 2349
• Page End: 2355
• Publication Date: 2018-03-15
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c7ob02346d
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : The synthesis of a new dimeric G-quadruplex-based DNA aptamer endowed with anti-HIV activity is reported. Abstract : By combining the ability of short G-rich oligodeoxyribonucleotides (ODNs) containing the sequence 5 ′CGGA 3 ′ to form higher order G-quadruplex (G4) complexes with the tetra-end-linked (TEL) concept to produce aptamers targeting the HIV envelope glycoprotein 120 (gp120), three new TEL-ODNs (1–3 ) having the sequence 5 ′CGGAGG 3 ′ were synthesized with the aim of studying the effect of G4 dimerization on their anti-HIV activity. Furthermore, in order to investigate the effect of the groups at the 5′ position, the 5′ ends of1–3 were left uncapped (1 ) or capped with either the lipophilic dimethoxytrityl (DMT) (2 ) or the hydrophilic glucosyl-4-phosphate (3 ) moieties. The here reported results demonstrate that only the DMT-substituted TEL-ODN2 is effective in protecting human MT-4 cell cultures from HIV infection (76% max protection), notwithstanding all the three new aptamers proved to be capable of forming stable higher order dimeric G4s when annealed in K + -containing buffer, thus suggesting that the recognition of a hydrophobic pocket on the target glycoprotein by the aptamers represents a main structural feature for triggering their anti-HIV activity.