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Specific herpes simplex virus-induced incorporation of 5-Iodo-5'-amino-2',5'-dideoxyuridine into deoxyribonucleic acid. [/sup 14/C, /sup 125/I tracer techniques]

Journal Article · · J. Biol. Chem.; (United States)
OSTI ID:6543551
; ;
5-Iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd) is a novel thymidine analog which inhibits herpes simplex virus, type 1 (HS-1 virus) replication in the absence of detectable host toxicity. When murine, simian, or human cells in culture are treated with (/sup 125/I)AIdUrd for up to 24 hours essentially none of the nucleoside becomes cell-associated. In contrast, upon HS-1 virus infection significant radiolabel is detected in both nucleotide pools and in DNA. The major acid-soluble metabolite has been shown by enzymic and chromatographic analysis to be the 5'-triphosphate of AIdUrd. DNA from HS-1 virus-infected Vero cells labeled with (/sup 14/C)thymidine, 5-(/sup 125/I)iodo-2'-deoxyuridine (IdUrd), or (/sup 125/I)AId-Urd was isolated by buoyant density centrifugation and subjected to digestion by pancreatic DNase I, spleen DNase II, micrococcal nuclease, spleen, and venom phosphodiesterases. Analysis of the digestion products clearly indicates that AIdUrd is incorporated internally into the DNA structure. DNA containing AIdUrd therefore contains phosphoramidate (P--N) bonds, known to be extremely acid-labile. The selective HS-1 virus-induced phosphorylation of AIdUrd and its subsequent incorporation into DNA may account for the unique biological activity of the AIdUrd nucleoside.
Research Organization:
Yale Univ., New Haven, CT
OSTI ID:
6543551
Journal Information:
J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 251:16; ISSN JBCHA
Country of Publication:
United States
Language:
English

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Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANTIMETABOLITES
ANTIMITOTIC DRUGS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
CARBON 14
CARBON ISOTOPES
CELL CULTURES
CHEMICAL ANALYSIS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA
DNA-ASE
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
ESTERASES
EVEN-EVEN NUCLEI
HERPES SIMPLEX
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROXY COMPOUNDS
INFECTIOUS DISEASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
IODODEOXYURIDINE
IODOURACILS
ISOTOPES
KINETICS
LIGHT NUCLEI
MICROORGANISMS
NUCLEI
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASITES
PHOSPHATASES
PYRIMIDINES
RADIOISOTOPES
REACTION KINETICS
RIBOSIDES
SKIN DISEASES
URACILS
VIRUSES
YEARS LIVING RADIOISOTOPES