Document 0492
 DOCN  M9550492
 TI    Minimal sequence requirements for synthetic peptides derived from the V3
       loop of the human immunodeficiency virus type 1 (HIV-1) to enhance HIV-1
       binding to cells and infection.
 DT    9505
 AU    Zanotto C; Calderazzo F; Dettin M; Di Bello C; Autiero M; Guardiola J;
       Chieco-Bianchi L; De Rossi A; Institute of Oncology, Interuniversity
       Center for Cancer; Research, Padova, Italy.
 SO    Virology. 1995 Feb 1;206(2):807-16. Unique Identifier : AIDSLINE
       MED/95159434
 AB    We previously demonstrated that a 23-mer peptide (DB3) derived from the
       V3 loop of the surface glycoprotein of HIV-1 MN strain was able to bind
       to soluble CD4 and enhance HIV-1 infection. The mechanism and structural
       features required for these biological activities were studied by using
       shortened DB3 derivatives and DB3 analogs carrying single amino acid
       substitutions. We found that peptides in which the aromatic amino acid
       in position 15 or 16 had been replaced by an uncharged hydrophobic
       residue (DB3-I15 and DB3-I16), analogs in which positively charged amino
       acids were replaced by corresponding D-enantiomers, and shortened
       DB3-derivatives lost both enhancing activity and ability to bind to
       soluble CD4. Other peptide variants in which a positively charged amino
       acid was replaced by asparagine at positions 3 (DB3-N3), 6 (DB3-N6), and
       19 (DB3-N19), respectively, retained both enhancing and binding
       activities, although with different efficiencies. The CD4 binder
       peptides DB3 and DB3-N19, but none of the CD4 nonbinder peptides,
       enhanced CD4 expression on peptide-treated cells as well as gp120
       binding to both CD4+ cells and soluble CD4. These findings strongly
       suggest that the peptide/CD4 interaction induced an increase in both CD4
       expression and CD4/gp120 binding affinity, which in turn mediated the
       enhancement of viral infection. A model of the structural conformation
       of DB3 peptide required for its biological activities is discussed.
 DE    Amino Acid Sequence  Antigens, CD/BIOSYNTHESIS/DRUG EFFECTS/*PHYSIOLOGY
       Antigens, CD4/BIOSYNTHESIS/DRUG EFFECTS/*PHYSIOLOGY  Binding Sites  Cell
       Line  Comparative Study  Dose-Response Relationship, Drug  Enzyme-Linked
       Immunosorbent Assay  Flow Cytometry  Human  HIV Core Protein
       p24/BIOSYNTHESIS/DRUG EFFECTS/*PHYSIOLOGY  HIV Envelope Protein
       gp120/*CHEMISTRY/DRUG EFFECTS/*METABOLISM  HIV-1/DRUG
       EFFECTS/*PHYSIOLOGY/PATHOGENICITY  Models, Structural  Molecular
       Sequence Data  Peptides/CHEMISTRY/CHEMICAL SYNTHESIS/*PHARMACOLOGY
       Protein Conformation  Structure-Activity Relationship  Support, Non-U.S.
       Gov't  T-Lymphocytes  Variation (Genetics)  JOURNAL ARTICLE

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