title: Tuning the hybridization properties of modified oligonucleotides: from flexible to conformationally constrained phosphonate internucleotide linkages.
abstract: The concept of conformational restriction leading to the preorganization of modified strands has proven to be successful and has afforded nucleic acid analogues with many interesting properties suitable for various biochemical applications. We utilized this concept to prepare a set of constrained oligonucleotides derived from 1,4-dioxane and 1,3-dioxolane-locked nucleoside phosphonates and evaluated their hybridization affinities towards their complementary RNA strands. With an increase of ΔTmper modification up to +5.2 °C, the hybridization experiments revealed the (S)-2',3'-O-phosphonomethylidene internucleotide linkage as one of the most Tm-increasing modifications reported to date. Moreover, we introduced a novel prediction tool for the pre-selection of potentially interesting chemical modifications of oligonucleotides.
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 2, 16610 Prague, Czech Republic. ivan.rosenberg@uochb.cas.cz.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Páv
authors.affiliation: Faculty of Mathematics and Physics, Institute of Physics, Charles University, Ke Karlovu 5, 12116 Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Barvík
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 2, 16610 Prague, Czech Republic. ivan.rosenberg@uochb.cas.cz.
authors.forename: Radek
authors.initials: R
authors.lastname: Liboska
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 2, 16610 Prague, Czech Republic. ivan.rosenberg@uochb.cas.cz.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Petrová
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 2, 16610 Prague, Czech Republic. ivan.rosenberg@uochb.cas.cz and Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 16628 Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Šimák
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 2, 16610 Prague, Czech Republic. ivan.rosenberg@uochb.cas.cz.
authors.forename: Šárka
authors.initials: Š
authors.lastname: Rosenbergová
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 2, 16610 Prague, Czech Republic. ivan.rosenberg@uochb.cas.cz.
authors.forename: Pavel
authors.initials: P
authors.lastname: Novák
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 2, 16610 Prague, Czech Republic. ivan.rosenberg@uochb.cas.cz.
authors.forename: Miloš
authors.initials: M
authors.lastname: Buděšínský
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS, Flemingovo náměstí 2, 16610 Prague, Czech Republic. ivan.rosenberg@uochb.cas.cz.
authors.forename: Ivan
authors.identifier: http://orcid.org/0000-0003-0921-9597
authors.initials: I
authors.lastname: Rosenberg
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry*
chemical_list: D009841:Oligonucleotides; D063065:Organophosphonates