title: 2,6-Bis(functionalized) purines as metal-ion-binding surrogate nucleobases that enhance hybridization with unmodified 2'-O-methyl oligoribonucleotides.
abstract: The capacity of three different purine bases, viz. 2,6-bis(3,5-dimethylpyrazol-1-yl)purine, 2-(3,5-dimethylpyrazol-1-yl)adenine and 2,6-bis(2-acetyl-1-methylhydrazino)purine, to form metal-ion mediated base pairs with the native nucleobases has been examined. For this purpose, ribonucleosides derived from these bases were incorporated into an intrastrand or a 3'-terminal position of short 2'-O-methyl oligoribonucleotides and the hybridization properties of these base modified oligomers in the absence and presence of three different metal ions (Cu(2+), Zn(2+) and Pd(2+)) were studied by UV- and CD-spectrometry. The first two bases were found to stabilize short oligonucleotide duplexes when incorporated into the 3'-termini of both strands, even in the absence of divalent metal ions but especially in the presence of Cu(2+). The highest melting temperature determined for such a duplex was 71.8 °C, nearly 30 °C higher than the T(m) of the respective solely Watson-Crick paired duplex. Despite the dramatic stabilizing effect of the terminal metallo-base pairs, these short modified oligonucleotides retained sequence-selectivity for the internal Watson-Crick base pairs: two internal mismatches dropped the melting temperature to 10-11 °C. In an internal position, only 2,6-bis(3,5-dimethylpyrazol-1-yl)purine, which in the absence of metal ions was destabilizing, exhibited metal-ion-dependent stabilization of duplex formation with unmodified 2'-O-methyl oligoribonucleotides. The melting temperature in the presence of Cu(2+) was increased from 6 to 14 °C, depending on the identity of the opposite base.
authors.affiliation: Department of Chemistry, University of Turku, FIN-20014Turku, Finland. shtahe@utu.fi
authors.forename: Sharmin
authors.initials: S
authors.lastname: Taherpour
authors.forename: Harri
authors.initials: H
authors.lastname: Lönnberg
authors.forename: Tuomas
authors.initials: T
authors.lastname: Lönnberg
mesh_terms: D002942:Circular Dichroism; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D015394:Molecular Structure; D009693:Nucleic Acid Hybridization; D009843:Oligoribonucleotides / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D011687:Purines / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D015032:Zinc / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D009843:Oligoribonucleotides; D009943:Organophosphorus Compounds; D011687:Purines; C434331:phosphoramidite; D010165:Palladium; D003300:Copper; D015032:Zinc