Triplex formation at physiological pH by oligonucleotides incorporating 5-Me-dC-(N4-spermine).
Oligonucleotide (ODN) directed triplex formation has therapeutic importance and depends on Hoogsteen hydrogen bonds between a duplex DNA and a third strand. While T*A:T triplets are formed at neutral pH, C+*G:C are favoured at acidic pH. Herein it is shown that 18-mer ODN containing spermine conjugated to 5-Me-dC at N4 (1-5), form triplexes with complementary 24-mer duplex 8:9 at neutral pH (7.3, 100 mM NaCl). Under such conditions, control ODN's carrying dC (6) or 5-Me-dC (7) did not show any triple helix formation. Remarkably, the triplexes from spermine-conjugates (1-5) have foremost stability at neutral pH (7.1), unlike the behavior of normal ODN's where optimal stability is at acidic pH (5.5). These results have importance in designing oligonucleotides for antigene applications.
Barawkar
D A
DA
Division of Organic Chemistry, National Chemical Laboratory, Pune, India.
Kumar
V A
VA
Ganesh
K N
KN
D001483:Base Sequence; D001665:Binding Sites; D015316:Genetic Therapy; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013696:Temperature
D009838:Oligodeoxyribonucleotides; D013096:Spermine