The influence of locked nucleic acid residues on the thermodynamic properties of 2′-O-methyl RNA/RNA heteroduplexes

被引:95
作者
Kierzek, E
Ciesielska, A
Pasternak, K
Mathews, DH
Turner, DH
Kierzek, R
机构
[1] Univ Rochester, Dept Chem, Rochester, NY 14627 USA
[2] Univ Rochester, Dept Pediat, Rochester, NY 14627 USA
[3] Polish Acad Sci, Inst Bioorgan Chem, PL-60714 Poznan, Poland
[4] Univ Rochester, Sch Med & Dent, Ctr Mol Pediat Res, Rochester, NY 14642 USA
[5] Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA
关键词
D O I
10.1093/nar/gki789
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:5082 / 5093
页数:12
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