Polyamine-functionalized 2'-amino-LNA in oligonucleotides: Facile synthesis of novel monomers and high affinity binding towards ssDNA and dsDNA.

In this study, polyamine functionalities were introduced into ONs via 2'-amino-LNA scaffolds. The resulting ONs exhibited efficient binding towards ssDNA, ssRNA and dsDNA targets, with the 2'-amino-LNA analogue carrying a tri-aminated linker showing the most pronounced duplex and triplex stabilizing effect. Molecular modelling revealed that favourable conformational and electrostatic effects led to the salt-bridge formed between positive-charged polyamine moieties and the Watson-Hoogsteen groove of the dsDNA targets, resulting in the observed triplex stabilization. All the investigated monomers conferred increased resistance against 3'-nucleolytic digestion relative to the non-functionalized controls. PMID: 33073896 [PubMed - as supplied by publisher]
Source: Chemistry - Category: Chemistry Authors: Tags: Chemistry Source Type: research