Major-groove-halogenated DNA: The effects of bromo and iodo substituents replacing H-C(7) of 8-aza-7-deazapurine-2,6-diamine or H-C(5) of uracil residues

Abstract

Oligonucleotides containing hatogenated `purine' and pyrimidine bases were synthesized. Bromo and iodo substituents were introduced at the 7-position of 8-aza-7-deazapurine-2,6-diamine (see 2b,c) or at the 5-position of uracil residues (see 3b,c). Phosphoramidites were synthesized after protection of 2b with the isobutyryl residue and of 2c with the benzoyl group. Duplexes containing the residues 2b or 2c gave always higher T, values than those of the nonmodified counterparts containing 2 ` -deoxyadenosine, the purine-2,6-diamine 2 ` -deoxyribonucleoside (1). or 2a at the same positions. Six 2b residues replacing dA in the duplex 5 ` -d(TAGGTCAATACT)-3 ` (11). 5 ` -d(AGTATTGACCTA)-3 ` (12) raised the T-m value from 48 to 75 degrees (4.5 degrees per modification ( Table 3)). Contrary to this. incorporation of the 5-halogenated 2 ` -deoxyuridines 3b or 3c into oligonucleotide duplexes showed very little influence on the thermal stability regardless of which `purine' nucleoside was located opposite to them ( Tables 4 and 5). The positive effects on the thermal stability of duplexes observed in DNA were also found in DNA RNA hybrids or in DNA with parallel chain orientation (Tables 8 and 9. resp.).