title: Effect of substituents of alloxazine derivatives on the selectivity and affinity for adenine in AP-site-containing DNA duplexes.
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 × 10(7) 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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan.
authors.forename: Burki
authors.initials: B
authors.lastname: Rajendar
authors.forename: Arivazhagan
authors.initials: A
authors.lastname: Rajendran
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ye
authors.forename: Eriko
authors.initials: E
authors.lastname: Kanai
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.forename: Seiichi
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Marek
authors.initials: M
authors.lastname: Sikorski
authors.forename: Norio
authors.initials: N
authors.lastname: Teramae
mesh_terms: D000225:Adenine / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D005415:Flavins / Q000737:chemistry / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011621:Pteridines / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence
chemical_list: D005415:Flavins; D008024:Ligands; D011621:Pteridines; C008173:isoalloxazine; D006147:Guanine; D004247:DNA; C006542:2-amino-4-hydroxypteridine; D000225:Adenine