Improvement of base selectivity and binding affinity by controlling hydrogen bonding motifs between nucleobases and isoxanthopterin: application to the detection of T/C mutation.
At an abasic site in an oligo-DNA duplex, isoxanthopterin (IX)(dagger) can bind to thymine (T) and cytosine (C) with strong affinity compared to adenine and guanine, but the base selectivity for T against C is moderate. In order to improve both binding affinity and base selectivity for T against C, a methyl group is introduced to IX, which is known as 3-methyl isoxanthopterin (3-MIX),(dagger) by which binding affinity for C is expected to decrease. Indeed, 3-MIX specifically binds to T more strongly than IX and loses its binding affinity for C. The improved binding ability of 3-MIX for T would be suitable for the practical use in SNP typing related to T.
Rajendar
Burki
B
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
Sato
Yusuke
Y
Nishizawa
Seiichi
S
Teramae
Norio
N
D020816:Amino Acid Motifs; D001482:Base Composition; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003596:Cytosine / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004252:DNA Mutational Analysis; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008956:Models, Chemical; D009154:Mutation; D013050:Spectrometry, Fluorescence; D013941:Thymine / Q000737:chemistry*; D014976:Xanthopterin / Q000737:chemistry*
C008217:isoxanthopterin; D003596:Cytosine; D004247:DNA; D013941:Thymine; D014976:Xanthopterin