Document 0505
 DOCN  M9590505
 TI    Synthesis of a photoaffinity analog of 3'-azidothymidine,
       5-azido-3'-azido-2',3'-dideoxyuridine. Interactions with herpesvirus
       thymidine kinase and cellular enzymes.
 DT    9509
 AU    Mao F; Rechtin TM; Jones R; Cantu AA; Anderson LS; Radominska A; Moyer
       MP; Drake RR; Department of Biochemistry and Molecular Biology,
       University of; Arkansas for Medical Sciences, Little Rock 72205, USA.
 SO    J Biol Chem. 1995 Jun 9;270(23):13660-4. Unique Identifier : AIDSLINE
       MED/95293956
 AB    Long term administration of 3'-azidothymidine (AZT) for the treatment of
       AIDS has led to detrimental clinical side effects in some patients, the
       biochemical causes of which are still being delineated.
       Base-substituted, azido-nucleotide photoaffinity analogs have routinely
       proven to be effective tools for identifying and characterizing
       nucleotide-utilizing enzymes. Therefore, we have synthesized
       5-azido-3'-azido-2',3'-dideoxyuridine, which is a potential
       photoaffinity analog of two human immunodeficiency virus drugs, AZT and
       3'azido-2',3'-dideoxyuridine. A partially purified herpes simplex virus
       type 1 thymidine kinase and [gamma-32P]ATP were used to make an AZT
       monophosphate analog, [32P]5-azido-3'-azido-2',3'-dideoxyuridine
       monophosphate. The photoaffinity properties of this analog were
       initially tested with herpes simplex virus type 1 thymidine kinase.
       Photoaffinity labeling of this enzyme was saturable (half-maximal, 30
       microM) and could be specifically inhibited by AZT, AZT monophosphate,
       thymidine, and thymidine monophosphate. Photolabeling of rat liver
       microsomal membranes was also done, and several membrane proteins that
       interact with AZT monophosphate were identified. The antiviral and
       cytotoxic activities of 5-azido-3'-azido-2',3'-dideoxyuridine were
       determined using human immunodeficiency virus, type 1 strain IIIB and an
       AZT drug-resistant strain in human T lymphocyte H9 cells.
 DE    Affinity Labels/*METABOLISM/PHARMACOLOGY  Animal  Antiviral
       Agents/CHEMICAL SYNTHESIS/*METABOLISM/PHARMACOLOGY  Herpesvirus 1,
       Human/*ENZYMOLOGY  HIV/DRUG EFFECTS  Microsomes, Liver/METABOLISM  Rats
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Thymidine
       Kinase/*METABOLISM  Zidovudine/*ANALOGS &
       DERIVATIVES/METABOLISM/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).