Document 0295
 DOCN  M9460295
 TI    Inhibition of human immunodeficiency virus type 1 reverse transcriptase
       dimerization using synthetic peptides derived from the connection
       domain.
 DT    9408
 AU    Divita G; Restle T; Goody RS; Chermann JC; Baillon JG; Max-Planck
       Institut fur Medizinische Forschung, Abteilung; Biophysik, Heidelberg,
       Federal Republic of Germany.
 SO    J Biol Chem. 1994 May 6;269(18):13080-3. Unique Identifier : AIDSLINE
       MED/94230400
 AB    Based on presently available information on the structure of human
       immunodeficiency virus type 1 (HIV-1) reverse transcriptase, peptides
       have been synthesized which correspond to the sequence of a particular
       region of the protein involved in formation of the active heterodimeric
       form of the enzyme. Several peptides that are 15-19 amino acids long and
       that are derived from the so-called connection domain of the reverse
       transcriptase are able to inhibit dimerization of the enzyme and thus
       inhibit development of its enzymatic activities. In particular, a
       tryptophan-rich 19-mer corresponding to residues 389-407 was relatively
       efficient, showing an apparent dissociation constant in the micromolar
       range for one or both of the subunits. The sequence of this region is
       identical for both subunits, since one (molecular mass of 51 kDa) is the
       proteolytic product of the other (molecular mass of 66 kDa).
       Dissociation of the preformed heterodimer could not be induced by the
       peptides, but increasing concentrations reduced the rate of dimerization
       in a concentration-dependent manner until it became immeasurable at high
       concentrations. The results suggest that inhibition of dimerization of
       reverse transcriptase is an attractive approach to chemotherapeutic
       intervention in HIV infection and that further development of
       peptide-based inhibition strategies is worth pursuing.
 DE    Amino Acid Sequence  Antiviral Agents/CHEMICAL SYNTHESIS/*PHARMACOLOGY
       Binding, Competitive  Cell Line  HIV-1/DRUG
       EFFECTS/*ENZYMOLOGY/PHYSIOLOGY  Molecular Sequence Data  Peptide
       Fragments/CHEMICAL SYNTHESIS/*PHARMACOLOGY  Polymers  Reverse
       Transcriptase/*ANTAGONISTS & INHIB/METABOLISM  Support, Non-U.S. Gov't
       Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

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