Synthesis and Reactivity of Aryl Nitrogen Mustard−Oligodeoxyribonucleotide Conjugates
| Autor: | Michael W. Reed, and Ansel Wald, Eugeny A. Lukhtanov, Alexander A. Gall, Vladimir V. Gorn, Igor V. Kutyavin, Rich B. Meyer |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Alkylation
Biomedical Engineering Pharmaceutical Science Bioengineering Buffers chemistry.chemical_compound Hydrolysis Drug Stability Nucleophile Hexylamine Nucleic Acids Organic chemistry Dimethyl Sulfoxide Reactivity (chemistry) Chromatography High Pressure Liquid Pharmacology Gel electrophoresis Base Sequence integumentary system Chemistry Aryl Organic Chemistry hemic and immune systems DNA respiratory system Nitrogen mustard Quaternary Ammonium Compounds Kinetics Oligodeoxyribonucleotides Solubility Nitrogen Mustard Compounds Nucleic Acid Conformation Biotechnology |
| Zdroj: | Bioconjugate Chemistry. 9:64-71 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc970134a |
| Popis: | A versatile method is described for preparing aryl nitrogen mustard-oligodeoxyribonucleotide (mustard-ODN) conjugates under anhydrous conditions. The chemistry uses DMSO soluble triethylammonium or tributylammonium salts of the ODNs. A G/A motif triplex forming ODN was chosen for study since it had been shown earlier to bind with high affinity and specificity to a duplex DNA target. A 5'-hexylamine derivative of this ODN was reacted with three different 2,3,5,6-tetrafluorophenyl ester derivatives of aryl nitrogen mustards which were designed to have different alkylation rates. An HPLC assay was used to determine reaction rates of these mustard-ODNs under various conditions. The reactivity of the mustard groups depended on chloride concentration and the presence of nucleophiles. Conjugation of mustards to G/A-containing ODNs decreased their aqueous stability. Hydrolysis and alkylation rates of these agents were consistent with reaction via an aziridinium intermediate. Rates of sequence specific alkylation within a triplex were determined by denaturing gel electrophoresis and shown to depend on inherent reactivity of the mustard group. The improved synthesis and chemical characterization of mustard-ODNs should facilitate their use as sequence specific alkylating agents and as probes for nucleic acid structure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|