Hybridization-promoted and cytidine-selective activation for cross-linking with the use of 2-amino-6-vinylpurine derivatives.
Recently, we have proposed a new concept for cross-linking agents with inducible reactivity, in which the highly reactive cross-linking agent, the 2-amino-6-vinylpurine nucleoside analogue (1), can be regenerated in situ from its stable precursors, the phenylsulfide (4) and the phenylsulfoxide (3) derivatives, by a hybridization-promoted activation process with selectivity to cytidine. The phenylsulfide precursor (4) exhibited cross-linking ability despite its high stability toward strong nucleophiles such as amines and thiols. In this study, we investigated the substituent effects of the phenylsulfide group on the cross-linking reaction, and determined the 2-carboxy substituent of the phenylsulfide derivative (11k) as an efficient cross-linking agent with inducible reactivity. Detailed investigations have shown that the phenylsulfoxide (3) and phenylsulfide (4) precursors produce the 2-amino-6-vinylpurine nucleoside (1) as the common reactive species. It has been concluded that the nature of the inducible reactivity of the precursors (3 and 4) is acceleration of their elimination to the 2-amino-6-vinylpurine nucleoside (1) through the selective process in the duplex with the ODN having cytidine at the target site.
Kawasaki
Takeshi
T
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Nagatsugi
Fumi
F
Ali
Md Monsur
MM
Maeda
Minoru
M
Sugiyama
Kumiko
K
Hori
Kenji
K
Sasaki
Shigeki
S
D020029:Base Pairing; D001483:Base Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003562:Cytidine / Q000737:chemistry*; D015195:Drug Design; D007202:Indicators and Reagents; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D011687:Purines / Q000737:chemistry*; D013440:Sulfides; D014753:Vinyl Compounds / Q000737:chemistry*
C432203:2-amino-6-vinylpurine; D003432:Cross-Linking Reagents; D007202:Indicators and Reagents; D009838:Oligodeoxyribonucleotides; D011687:Purines; D013440:Sulfides; D014753:Vinyl Compounds; D003562:Cytidine