Effect of an alkyl amino group on the binding of 1,8-naphthyridines to AP site-containing DNA duplexes.
A 1,8-naphthyridine derivative having a positively charged side-chain, N-(3-aminopropyl)-5,6,7-trimethyl-1,8-naphthyridine-2-amine (APATMND), is synthesized, and its binding to AP site-containing DNA duplexes (5'- GCA GCT CCC GXG GTC TCC TCG-3'/ 5'-CGA GGA GAC CNC GGG AGC TGC-3', X = AP site; dSpacer, N = C, T) is examined in solutions buffered to pH 7.0 (I = 0.11 M, at 20 degrees C). Fluorescence titration experiments reveal that, as compared to a parent ligand, 2-amino-5,6,7-trimethyl-1,8-naphthyridine (ATMND), capable of selectively binding C over T opposite an AP site in the duplex (K(d)/nM: C: 56, T: 100), APATMND shows a stronger binding affinity for T, while an affinity for C is reduced (K(d)/nM: C: 135, T: 37). An examination of salt dependence of binding constants reveals that a polyelectrolyte contribution (Delta G(pe)) is indeed increased for C- and T-bindings of APATMND, but a loss of non-polyelectrolyte contribution (Delta G(t)) is significant when binding to C. These binding properties of APATMND are discussed with a view towards further development of DNA-binding ligands suitable for gene detection.
Ichihashi
Toshiki
T
Department of Chemistry, Graduate School of Science, Tohoku Univerisity, and CREST, Japan Science and Technology Agency (JST), Aoba-ku, Sendai 980-8578, Japan.
Sato
Yusuke
Y
Seino
Takehiro
T
Nishizawa
Seiichi
S
Teramae
Norio
N
D003596:Cytosine / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D008024:Ligands; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013941:Thymine / Q000737:chemistry
C528376:2-amino-5,6,7-trimethyl-1,8-naphthyridine; D008024:Ligands; C541616:N-(3-aminopropyl)-5,6,7-trimethyl-1,8-naphthyridine-2-amine; D009287:Naphthyridines; D003596:Cytosine; D004247:DNA; D013941:Thymine