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Oligonucleotides with Cationic Backbone and Their Hybridization with DNA: Interplay of Base Pairing and Electrostatic Attraction
Author(s) -
Schmidtgall Boris,
Kuepper Arne,
Meng Melissa,
Grossmann Tom N.,
Ducho Christian
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201704338
Subject(s) - oligonucleotide , cationic polymerization , base pair , dna , pairing , chemistry , molecular structure of nucleic acids: a structure for deoxyribose nucleic acid , stereochemistry , biophysics , combinatorial chemistry , biochemistry , biology , physics , organic chemistry , superconductivity , quantum mechanics
Non‐natural oligonucleotides represent important (bio)chemical tools and potential therapeutic agents. Backbone modifications altering hybridization properties and biostability can provide useful analogues. Here, we employ an artificial nucleosyl amino acid (NAA) motif for the synthesis of oligonucleotides containing a backbone decorated with primary amines. An oligo‐T sequence of this cationic DNA analogue shows significantly increased affinity for complementary DNA. Notably, hybridization with DNA is still governed by Watson–Crick base pairing. However, single base pair mismatches are tolerated and some degree of sequence‐independent interactions between the cationic NAA backbone and fully mismatched DNA are observed. These findings demonstrate that a high density of positive charges directly connected to the oligonucleotide backbone can affect Watson–Crick base pairing. This provides a paradigm for the design of therapeutic oligonucleotides with altered backbone charge patterns.