Bioorganic & Medicinal Chemistry Letters 2007-07-01

Improvement of base selectivity and binding affinity by controlling hydrogen bonding motifs between nucleobases and isoxanthopterin: application to the detection of T/C mutation.

Burki Rajendar, Yusuke Sato, Seiichi Nishizawa, Norio Teramae

Index: Bioorg. Med. Chem. Lett. 17(13) , 3682-5, (2007)

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Abstract

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.