Acid-mediated cleavage of oligonucleotide P3' --> N5' phosphoramidates triggered by sequence-specific triplex formation.
The P-N bond in oligonucleotide P3' --> N5' phosphoramidates (5'-amino-DNA) is known to be chemoselectively cleaved under mild acidic conditions. We prepared homopyrimidine oligonucleotides containing 5'-amino-5'-deoxythymidine (5'-amino-DNA thymine monomer) or its conformationally locked congener, 5'-amino-2',4'-BNA thymine monomer, at midpoint of the sequence. The effect of triplex formation with homopurineohomopyrimidine dsDNA targets on acid-mediated hydrolysis of the P3' --> N5' phosphoramidate linkage was evaluated. Very interestingly, it was found that the triplex formation significantly accelerates the P-N bond cleavage.
Obika
Satoshi
S
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Tomizu
Masaharu
M
Negoro
Yoshinori
Y
Osaki
Tomohisa
T
Orita
Ayako
A
Ueyama
Yuji
Y
Nakagawa
Osamu
O
Imanishi
Takeshi
T
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D001483:Base Sequence; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000577:Amides; D001952:Bridged-Ring Compounds; D009838:Oligodeoxyribonucleotides; D010756:Phosphoric Acids; C011067:phosphoramidic acid