The influence of locked nucleic acid residues on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes.
The influence of locked nucleic acid (LNA) residues on the thermodynamic properties of 2'-O-methyl RNA/RNA heteroduplexes is reported. Optical melting studies indicate that LNA incorporated into an otherwise 2'-O-methyl RNA oligonucleotide usually, but not always, enhances the stabilities of complementary duplexes formed with RNA. Several trends are apparent, including: (i) a 3' terminal U LNA and 5' terminal LNAs are less stabilizing than interior and other 3' terminal LNAs; (ii) most of the stability enhancement is achieved when LNA nucleotides are separated by at least one 2'-O-methyl nucleotide; and (iii) the effects of LNA substitutions are approximately additive when the LNA nucleotides are separated by at least one 2'-O-methyl nucleotide. An equation is proposed to approximate the stabilities of complementary duplexes formed with RNA when at least one 2'-O-methyl nucleotide separates LNA nucleotides. The sequence dependence of 2'-O-methyl RNA/RNA duplexes appears to be similar to that of RNA/RNA duplexes, and preliminary nearest-neighbor free energy increments at 37 degrees C are presented for 2'-O-methyl RNA/RNA duplexes. Internal mismatches with LNA nucleotides significantly destabilize duplexes with RNA.
Kierzek
Elzbieta
E
Department of Chemistry, University of Rochester RC Box 270216, Rochester, NY 14627-0216, USA.
Ciesielska
Anna
A
Pasternak
Karol
K
Mathews
David H
DH
Turner
Douglas H
DH
Kierzek
Ryszard
R
D020137:Base Pair Mismatch; D008745:Methylation; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D009843:Oligoribonucleotides / Q000737:chemistry*; D020871:RNA Stability; D012330:RNA, Double-Stranded / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry; D013816:Thermodynamics
D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides; D012330:RNA, Double-Stranded; C477371:locked nucleic acid; D012965:Sodium Chloride