Synthesis and binding properties of oligo-2'-deoxyribonucleotides conjugated with triple-helix-specific intercalators: benzo[e] and benzo[g] pyridoindoles.
DNA binding compounds, such as benzo[e] (BePI) and benzo[g] pyridoindole (BgPI) derivatives, exhibit preferential stabilization of triple helices. We report here the synthesis of a series of pyrimidine triple-helix-forming oligo-2'-deoxyribonucleotides conjugated with these molecules. BePI was coupled to the 5-position of 2'-deoxyuridine via two linkers of different sizes attached to its 11-position and placed at either the 5'-end, inside the sequence, or at both the 5'-end and the internal positions using periodate oxidation of a diol-containing oligonucleotide followed by reductive coupling with amino-linked BePI. The same BePI derivatives were also linked to the oligonucleotide chain via internucleotidic phosphorothiolate or phosphoramidate linkages. A mixture of diastereoisomers was prepared as well as separate pure Rp and Sp isomers. A BePI derivative, with two different linkers attached to its 3-position, and BgPI derivatives were also linked to the 5-position of a 2'-deoxyuridine located at either the 5'-end or inside the sequence, as well as to the beta- anomeric position of an additional 2'- deoxyribose placed inside the sequence. The binding properties of these oligonucleotide-benzopyridoindoles conjugates with their double-stranded DNA target was studied by absorption spectroscopy.
Vinogradov
Serguei
S
Centre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, 45071 Orléans Cedex 02, France.
Roig
Victoria
V
Sergueeva
Zinaida
Z
Nguyen
Chi Hung
CH
Arimondo
Paola
P
Thuong
Nguyen T
NT
Bisagni
Emile
E
Sun
Jian-Sheng
JS
Hélène
Claude
C
Asseline
Ulysse
U
D001483:Base Sequence; D003432:Cross-Linking Reagents; D004247:DNA; D007211:Indoles / Q000737:chemistry*; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D020319:Oligodeoxyribonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry; D013053:Spectrophotometry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D003432:Cross-Linking Reagents; D007211:Indoles; D007364:Intercalating Agents; D020319:Oligodeoxyribonucleotides, Antisense; C051802:triplex DNA; D004247:DNA