CD4-modified synthetic peptides containing phenylalanine inhibit HIV-1 infection in vitro.
Phenylalanine-containing peptides from CD4 were synthesized based on chemical similarity with active CD4(81-92)-benzylated peptides. The synthetic peptide FYIFFVEDQKEEDD blocked the binding of gp120 to CD4 and inhibited 50% human immunodeficiency virus (HIV)-induced syncytia formation at a concentration (IC50) of approximately 40-50 microM and HIV p17 expression with an IC50 of approximately 67 microM. The peptide is not toxic to cells in vitro. Moreover, acute toxicity studies carried out in Swiss mice showed the peptide to be nontoxic at a dose of 2,000 mg/kg. This phenylalanine-substituted CD4 peptide may prove to be useful in the treatment of AIDS.
Lasarte
J J
JJ
Departamento de Medicina Interna, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain.
Sarobe
P
P
Golvano
J
J
Prieto
I
I
Civeira
M P
MP
Gullón
A
A
Sarin
P S
PS
Prieto
J
J
Borrás-Cuesta
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015683:Gene Products, gag / Q000096:biosynthesis / Q000187:drug effects; D015726:Giant Cells / Q000382:microbiology; D015488:HIV Antigens / Q000096:biosynthesis / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D010649:Phenylalanine / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015683:Gene Products, gag; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D010455:Peptides; D011994:Recombinant Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D010649:Phenylalanine