Effective modulation of DNA duplex stability by reversible transition metal complex formation in the minor groove.
Herein we describe the reversible changing of DNA duplex thermal stability by exploiting transition metal complexation phenomena. A terpyridine ligand was conjugated to the N2'-atoms of 2'-amino-2'-deoxyuridine and its locked counterpart 2'-amino-LNA, and these metal-complexing monomers were incorporated into oligodeoxyribonucleotides. Upon addition of varying amounts of transition metal ions, the thermal stability of DNA duplexes containing these terpyridine-functionalized units in different constitutions was affected to different degrees (DeltaTm values = -15.5 to +49.0 degrees C, relative to the unmodified duplex). The most pronounced effects were observed when two complexing monomers were positioned in opposite strands. Addition of 1 equiv of Ni2+ to such a system induced extraordinary duplex stabilization. Molecular modeling studies suggest, as an explanation for this phenomenon, formation of nickel-mediated interstrand linkages in the minor groove. Addition of an excess of metal ions resulted in largely decreased Tm values. Alternating addition of metal ions and EDTA demonstrated reversibility of metal ion-induced changes in hybridization strength, proving that the described approach provides an efficient method for duplex stability modulation.
Kalek
Marcin
M
Nucleic Acid Center, Department of Physics and Chemistry, University of Southern Denmark, Odense M, Denmark.
Madsen
Andreas S
AS
Wengel
Jesper
J
D002412:Cations; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000737:chemistry; D004492:Edetic Acid / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D009532:Nickel / Q000494:pharmacology; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D013696:Temperature; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives / Q000737:chemistry; D028561:Transition Elements / Q000737:chemistry*
C410434:2'-amino-2'-deoxyuridine; C520121:7-(2-cyanoethoxy(diisopropylamino)phosphinoxy)-1-(4,4'-dimethoxytrityloxymethyl)-5-(9'-fluorenylmethoxycarbonyl)-3-(thymin-1-yl)-2-oxa-5-azabicyclo(2.2.1)heptane; D002412:Cations; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D009942:Organometallic Compounds; D011725:Pyridines; D028561:Transition Elements; D013938:Thymidine Monophosphate; D009532:Nickel; D004247:DNA; D004492:Edetic Acid; D003857:Deoxyuridine