Publicaciones científicas

Further insights on the inhibition of HIV type 1 infection in vitro by CD4-modified synthetic peptides containing phenylalanine

Prieto I, Lasarte JJ, Sarobe P, Golvano J, Civeira MP, Gullón A, Prieto J, Borrás-Cuesta F.
Departamento de Medicina Interna, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain.

Revista: AIDS Research and Human Retroviruses

Fecha: 01/07/1996

Medicina Interna

Phenylalanine-containing peptides from CD4 were synthesized on the basis of chemical similarity with active CD4(81-92)-benzylated peptides. Systematic replacement of amino acids of these peptides bearing the benzyl group by phenylalanine, afforded several peptides that were able to block the binding of gp120 to CD4 and to inhibit HIV-induced syncytium formation. These experiments showed that substitution of residues 81 and 85 by phenylalanine was the most important for activity.

Following optimization of the length of phenylalanine-substituted peptides it was found that FYICFVED and FYICFVEDE were the most active. Their IC50 for the inhibition of syncytium formation was around 1.2-1.6 microM. This activity is at least 30 times higher than that of the parent peptide FYIFFVEDQKEEDD previously reported (Lasarte et al., J Acquir Immune Defic Syndr 1994;7:129-134). Binding competition experiments with two different anti-peptide antisera recognizing the V3 region of gp120 and FYICFVEDE, show that the active peptides bind to V3 or to a sterically near region of V3. None of the active peptides was toxic to cells in vitro.

The enhanced activity and simplicity of these new phenylalanine-substituted CD4 peptides might be a good starting point for the development of mimotopes of potential use for the treatment of AIDS.

CITA DEL ARTÍCULO  AIDS Res Hum Retroviruses. 1996 Jul 20;12(11):1023-30

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