Improved selectivity for the binding of naphthyridine dimer to guanine-guanine mismatch.
Naphthyridine dimer composed of two 2-amino-1,8-naphthyridines and a connecting linker strongly binds to guanine-guanine (G-G) mismatch in duplex DNA. In order to improve G-G selectivity for the binding, we have examined structure modification of the linker. A new naphthyridine dimer possessing 3,6-diazaoctanedioic acid linker binds to G-G mismatch with an association constant of 1.18 x 10(7) M(-1), which is somewhat weaker than that of the original naphthyridine dimer having a shorter connecting linker. However, the binding of the modified naphthyridine dimer to G-A mismatch was almost negligible as compared to that of the original. This results in a net increase of the selectivity for the binding to G-G mismatch by 4-folds.
Nakatani
K
K
Department of Synthetic Chemistry and Biological Chemistry, Faculty of Engineering, Kyoto University, CREST, Kyoto 606-8501, Japan. nakatani@sbchem.Kyoto-u.ac.jp
Sando
S
S
Saito
I
I
D020137:Base Pair Mismatch; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000494:pharmacology; D018983:DNA Footprinting; D019281:Dimerization; D015195:Drug Design; D006147:Guanine / Q000378:metabolism*; D007700:Kinetics; D009287:Naphthyridines / Q000737:chemistry / Q000378:metabolism*; D009691:Nucleic Acid Denaturation; D009692:Nucleic Acid Heteroduplexes; D013696:Temperature; D017186:Titrimetry
D003432:Cross-Linking Reagents; D009287:Naphthyridines; D009692:Nucleic Acid Heteroduplexes; D006147:Guanine