Purine-Derived Nitroxides for Noncovalent Spin-Labeling of Abasic Sites in Duplex Nucleic Acids
| Autor: | Nilesh R. Kamble, Snorri Th. Sigurdsson |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Guanine Stereochemistry 010402 general chemistry 01 natural sciences Catalysis Cyclic N-Oxides 03 medical and health sciences chemistry.chemical_compound Cytosine Nucleic Acids AP site Spin label 2-Aminopurine Nuclear Magnetic Resonance Biomolecular Molecular Structure Adenine Organic Chemistry General Chemistry Site-directed spin labeling DNA 0104 chemical sciences Thymine 030104 developmental biology chemistry Purines Nucleic acid RNA Spin Labels |
| Zdroj: | Chemistry (Weinheim an der Bergstrasse, Germany). 24(16) |
| ISSN: | 1521-3765 |
| Popis: | A series of purine-based spin labels was prepared for noncovalent spin-labeling of abasic sites of duplex nucleic acids through hydrogen bonding to an orphan base on the opposing strand and π-stacking interactions with the flanking bases. Both 1,1,3,3-tetramethylisoindolin-2-yloxyl and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) were conjugated to either the C2- or C6-position of the purines, yielding nitroxide derivatives of guanine, adenine, or 2,6-diaminopurine. The isoindoline-derived spin labels showed extensive or full binding to abasic sites in RNA duplexes, whereas the TEMPO-derived spin labels showed limited binding. An adenine-derived spin label (5) bound fully at low temperature to abasic sites in both DNA and RNA duplexes when paired with thymine and uracil, respectively, complementing the previously described guanine-derived spin label Ǵ, which binds efficiently opposite cytosine. Compound Ǵ was also shown to bind to abasic sites in DNA-RNA hybrids, either in the DNA- or the RNA-strand. Ǵ showed only a minor flanking-sequence effect upon binding to abasic sites in RNA. When the abasic site was placed close to the end of the RNA duplex, the affinity of the spin label Ǵ was reduced; full binding was observed at the fourth position from the duplex end. In summary, spin labels 5 and Ǵ showed full binding to abasic sites in both DNA and RNA duplexes and are promising spin labels for structural studies of nucleic acids by pulsed EPR methods. |
| Databáze: | OpenAIRE |
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