Preparation and characterization of oligonucleotides containing S-(2-(N sup 7 -guanyl)ethyl)glutathione
- Vanderbilt Univ., Nashville, TN (United States)
S-(2-(N{sup 7}-Guanyl)ethyl)glutathione is the major adduct derived from modification of DNA with 1,2-dibromoethane in biological systems and is postulated to be a mutagenic lesion. Oligonucleotides containing this modified base were prepared by treatment of oligonucleotides with S-(2-chloroethyl)glutathione and purified by chromatography. The oligomer d-(C{sub 1}A{sub 2}T{sub 3}G{sub 4}C{sub 5}C{sub 6}T{sub 7}) was modified to contain a single S-(2-(N{sup 7}-guanyl)ethyl)glutathione moiety at the central position, and UV, CD, and {sup 1}H NMR studies indicated that this oligomer hybridized to its normal complement d(A{sub 8}G{sub 9}G{sub 10}C{sub 11}A{sub 12}T{sub 13}G{sub 14}), although the binding was considerably weakened by adduction. All proton resonances were identified using two-dimensional {sup 1}H NMR spectroscopy. These results suggest that a rather local structural perturbation occurs in the DNA oligomer upon modification and that the glutathione moiety appears to be relatively unperturbed by its placement in the duplex. The authors conclude that these N{sup 7}-guanyl derivatives destabilize hybridization and that bases other than cytosine do not appear to show preferential thermodynamic bonding to these adducts, at least in the sequences examined to date.
- OSTI ID:
- 5616201
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:43; ISSN 0006-2960; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ADDUCTS
ALKYLATING AGENTS
BIOLOGICAL EFFECTS
DICHROISM
DNA ADDUCTS
DNA HYBRIDIZATION
DRUGS
GLUTATHIONE
HYBRIDIZATION
MAGNETIC CIRCULAR DICHROISM
MAGNETIC RESONANCE
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RESONANCE