2'-O-[2-(guanidinium)ethyl]-modified oligonucleotides: stabilizing effect on duplex and triplex structures.
[structure: see text] Oligonucleotides with a novel 2'-O-[2-(guanidinium)ethyl] (2'-O-GE) modification have been synthesized using a novel protecting group strategy for the guanidinium group. This modification enhances the binding affinity of oligonucleotides to RNA as well as duplex DNA (DeltaT(m) 3.2 degrees C per modification). The 2'-O-GE modified oligonucleotides exhibited exceptional resistance to nuclease degradation. The crystal structure of a palindromic duplex formed by a DNA oligonucleotide with a single 2'-O-GE modification was solved at 1.16 A resolution.
Prakash
Thazha P
TP
Department of Medicinal Chemistry, Isis Pharmaceuticals, Inc., Carlsbad, California 92008, USA.
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A
Lesnik
Elena
E
Mohan
Venkatraman
V
Tereshko
Valentina
V
Egli
Martin
M
Manoharan
Muthiah
M
D004247:DNA / Q000737:chemistry*; D018076:DNA, Complementary / Q000737:chemistry; D019791:Guanidine / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D018075:RNA, Complementary / Q000737:chemistry; D013997:Time Factors
D018076:DNA, Complementary; D009841:Oligonucleotides; D018075:RNA, Complementary; D012313:RNA; D004247:DNA; D019791:Guanidine