Assessment of the sequence dependency for the binding of 2-aminonaphthyridine to the guanine bulge.
We have studied the sequence dependent binding of 2-amino-1,8-naphthyridine derivative 1 to a single guanine bulge. The free energy changes for the binding to a guanine bulge with different sequence contexts (5'X_Y3'/3'X'GY'5') were determined by a curve fitting of the thermal denaturation profile of DNA in the presence and absence of 1. The data showed that (i) the binding of 1 to a guanine bulge is stronger for those flanking the G-C base pair than A-T base pair, (ii) the guanine 3' side to 1 in the complex is especially effective for the complex stabilization, and (iii) the increase of T(m) in the presence of 1 is not a good estimate for the sequence dependent binding. The most efficient 1-binding was observed for the sequence of G_G/CGC. Molecular modeling simulations suggested that stacking interaction between the 3' side guanine and 1 is the molecular basis for the strong binding to G_G/CGC.
Nakatani
Kazuhiko
K
Department of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering, Kyoto University, Kyoto 606-8501, Japan. nakatani@sbchem.kyoto-u.ac.jp
Horie
Souta
S
Murase
Takashi
T
Hagihara
Shinya
S
Saito
Isao
I
D001482:Base Composition; D020137:Base Pair Mismatch; D001483:Base Sequence; D001665:Binding Sites; D006147:Guanine / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013696:Temperature
C427025:2-amino-1,8-naphthyridine; D007364:Intercalating Agents; D009287:Naphthyridines; D006147:Guanine