Characterization of a unique scrambled peptide derived from the CD4 CDR3-related region which shows substantial activity for blocking HIV-1 infection.
We have previously identified CD4 peptides that exhibited blocking activity on human immunodeficiency virus type 1 (HIV-1) infection, i.e. CD4(68-130) and CD4(66-92) which include the region corresponding to the third complementarity-determining region of IgG. Here we describe a unique peptide derived from CD4(66-92), altered in amino acid sequence but not in composition, which was found to have increased anti-HIV-1 activity. The acidic amino acid residues in this scrambled peptide, S1, localized at the N-terminus, while in the native peptide they clustered at the C-terminus. On the other hand, a second scrambled peptide, S2, in which the acidic amino acid residues were fully dispersed, did not show any anti-HIV-1 activity. However, we could not identify any correlation between CD4(66-92) and S1 peptides by their hydrophobic or circular dichroism spectrum analyses. The results provide insight into the mechanisms of HIV-1 gp120 and CD4 interaction and may be useful as a new approach to AIDS therapy.
Ohki
K
K
Section of Serology, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Kumagai
K
K
Mitsuda
S
S
Takano
T
T
Kimura
T
T
Ikuta
K
K
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D015704:CD4 Antigens / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D015704:CD4 Antigens; C081945:CD4 S1 peptide; D010446:Peptide Fragments