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Issue 21, 2010
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Effect of substituents of alloxazine derivatives on the selectivity and affinity for adenine in AP-site-containing DNA duplexes

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Abstract

Using the DNA duplex containing an AP site (5′-TCC AGX GCA AC-3′/3′-AGG TCN CGT TG-5′, X = AP site, N = A, T, C, or G), we have found that 2-amino-4-hydroxypteridine (pterin) selectively binds to guanine (G), and that the enhanced binding affinity for G is obtained by its methylated derivative 2-amino-6,7-dimethyl-4-hydroxypteridine (diMe pteridine). Similarly, among the cytosine (C)-selective ligands, i.e. derivatives of 2-amino-1,8-naphthyridine, a trimethyl-substituted derivative (2-amino-5,6,7-trimethyl-1,8-naphthyridine) selectively binds to C with a strong binding affinity of 1.9 × 107 M−1. In the case of lumazine derivatives, pteridine-2,4(1H,3H)-dione (lumazine) binds to adenine (A), and its methylated derivative, 6,7-dimethylpteridine-2,4(1H,3H)-dione (diMe lumazine) strongly binds to A with enhanced binding affinity, keeping the same base-selectivity. On the other hand, the benzo-annelated (with phenyl ring, 2.4 Å) derivative of lumazine, benzo[g]pteridine-2,4(1H,3H)-dione (alloxazine), can bind to A selectively, whereas its methylated ligand, 7,8-dimethylbenzo[g]pteridine-2,4(1H,3H)-dione (lumichrome) selectively binds to thymine (T) over A, C and G. Methyl-substituted lumichrome derivatives show moderate binding affinities for target nucleobases. The changes in the base-selectivity and binding affinities are discussed in detail with respect to the substituents of these ligands, considering hydrogen-bonding patterns, size of AP site and stacking interactions.

Graphical abstract: Effect of substituents of alloxazine derivatives on the selectivity and affinity for adenine in AP-site-containing DNA duplexes

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Supplementary files

Article information


Submitted
29 Apr 2010
Accepted
15 Jul 2010
First published
31 Aug 2010

Org. Biomol. Chem., 2010,8, 4949-4959
Article type
Paper

Effect of substituents of alloxazine derivatives on the selectivity and affinity for adenine in AP-site-containing DNA duplexes

B. Rajendar, A. Rajendran, Z. Ye, E. Kanai, Y. Sato, S. Nishizawa, M. Sikorski and N. Teramae, Org. Biomol. Chem., 2010, 8, 4949
DOI: 10.1039/C0OB00057D

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