Document 0337
 DOCN  M9440337
 TI    The amino-terminal peptide of HIV-1 gp41 interacts with human serum
       albumin.
 DT    9404
 AU    Gordon LM; Curtain CC; McCloyn V; Kirkpatrick A; Mobley PW; Waring AJ;
       Department of Pediatrics, Drew University, King Medical; Center/UCLA
       90059.
 SO    AIDS Res Hum Retroviruses. 1993 Nov;9(11):1145-56. Unique Identifier :
       AIDSLINE MED/94145750
 AB    Structural and functional studies were made to assess interactions
       between human serum albumin (HSA) and the amino-terminal peptide (FP-I;
       23-residue peptide 519-541) of glycoprotein 41,000 (gp41) of human
       immunodeficiency virus type-1 (HIV-1). Circular dichroism (CD)
       spectroscopy indicated that the peptide binds to albumin with dominant
       alpha-helical character. Peptide binding to albumin was also examined
       using FP-I spin labeled at either the amino-terminal alanine (FP-II;
       residue 519) or methionine (FP-III; position 537). Electron spin
       resonance (ESR) spectra of FP-II bound to HSA at 38 degrees C indicated
       that the spin label at the amino-terminal residue (Ala-519) was
       motionally restricted. The ESR spectrum of 12-nitroxide stearate
       (12-NS)-labeled HSA was identical to that obtained with FP-II,
       indicating that the reporter groups for the 12-NS and FP-II probes are
       similarly bound to albumin. Contrarily, ESR spectra of HSA labeled with
       FP-III indicated high mobility for the reporter group (Met-537) at the
       aqueous-protein interface. This suggests that the N-terminal gp41
       peptide binds as an alpha helix (residues 519-536) to fatty acid sites
       on HSA, such that Ala-519 of the peptide residues in the interior of the
       protein while Met-537 lies outside the protein in aqueous solution. It
       is also of interest that addition of HSA to human red blood cells
       dramatically reduced the ability of FP-I to induce hemolysis, presumably
       through peptide-albumin binding that inhibited FP-I interactions with
       red cell membranes. The significance of these results focuses on the
       following three points. The first is that high serum levels of albumin
       may limit the efficacy of anti-HIV therapies using peptides based on the
       N-terminal gp41 domain. The second is that the elucidation of FP-I and
       HSA interactions with physical techniques may provide clues on the
       molecular features underlying viral FP-I combination with receptors on
       the target cell surface. Last, the affinity of albumin for the
       N-terminal gp41 peptide may play a subordinate role in the blocking of
       HIV infectivity in vitro that has been reported for chemically modified
       albumins.
 DE    Amino Acid Sequence  Antiviral Agents/PHARMACOLOGY  Binding
       Sites/GENETICS  Circular Dichroism  Electron Spin Resonance Spectroscopy
       Hemolysis  Human  HIV Envelope Protein
       gp41/CHEMISTRY/GENETICS/*METABOLISM  HIV-1/DRUG
       EFFECTS/GENETICS/*METABOLISM  In Vitro  Molecular Sequence Data
       Peptides/PHARMACOLOGY  Protein Binding  Protein Structure, Secondary
       Serum Albumin/CHEMISTRY/*METABOLISM  Spin Labels  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

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