Synthesis of alkylating oligonucleotide derivatives containing cholesterol or phenazinium residues at their 3′-terminus and their interaction with DNA within mammalian cells

• Published in: FEBS letters Vol. 254; no. 1; pp. 129 - 132
• Main Authors: Boutorin, A.S., Gus'kova, L.V., Ivanova, E.M., Kobetz, N.D., Zarytova, V.F., Ryte, A.S., Yurchenko, L.V., Vlassov, V.V.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28-08-1989; Elsevier
• Subjects: [4-(N-2-chloroethyl)N-methylaminobenzyl]-amine; adenosine 5′-triphosphate; Alkylating Agents - analysis; Alkylating Agents - chemical synthesis; Alkylating Agents - pharmacology; Analytical, structural and metabolic biochemistry; Animals; ATP; Binding Sites; Biological and medical sciences; Carcinoma - analysis; Cholesterol - pharmacology; ClRCH2NH2; DNA affinity modification; DNA, Neoplasm - analysis; DNA-Binding Proteins - analysis; Fibroblasts - analysis; Fundamental and applied biological sciences. Psychology; Hydrophobic group; Mice; Nucleic acids; Nucleic bases, nucleotides; Oligonucleotide uptake; Oligonucleotides - analysis; Oligonucleotides - chemical synthesis; Oligonucleotides - pharmacology; Phenazines - pharmacology; Polyaromatic group; Reactive oligonucleotide derivative; DNA affinity modification; Oligonucleotide uptake; Hydrophobic group; Polyaromatic group; Reactive oligonucleotide derivative; ATP; ClRCH 2NH 2; Aromatic compound; Oligonucleotide
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(89)81023-3

5′-[
32P]-labelled alkylating decathymidylate [4-(
N-2-chloroethyl)
N-methylaminobenzyl]-5′-phosphamide derivatives containing cholesterol or phenazinium residues at their 3′-termini were synthesized and used for alkylation of DNA within mammalian cells. The uptake of the cholesterol derivative by the cells and the extent of DNA alkylation are about two orders of magnitude higher than those of a similar alkylating derivative lacking the groups at the 3′-termini. The presence of the phenazinium residue at the 3′-terminus of the oligonucleotide reagent does not improve the reagent uptake by the cells but drastically increases the DNA modification efficiency.