Anti-HIV activity of N-(2,3-dihalogenopropyl)- and N-allyl-glycine containing pentapeptides

• Published in: Bioorganic & medicinal chemistry letters 1994-11, Vol.4 (21), p.2533-2537
• Main Authors: Wakselman, Michel, Mouna, Abdel Malek, Xie, Juan, Mazaleyrat, Jean-Paul, Boulay, Raymond, Lelièvre, Yves, Bousseau, Anne, Nachmansohn, Chantal, Hénin, Yvette
• Format: Article
• Language: English
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)80278-X

A series of peptides containing N-(2,3-dihalopropyl)-glycine or alanine residues has been prepared as potential suicide substrates of the HIV pol-protease or as enzyme-activated prodrugs. Halogenation of unsaturated N-allyl peptide precursors in dichloromethane occurs with participation of a neighboring amide group and leads to halohydrins instead of the expected dihalides. Use of X 2/ LiX/HOAc conditions gives the desired dihalogenated derivatives. These functionalized substrate analogs are not inhibitors of the enzyme. However, Boc-Ala-Phe- N-(2,3-dihalogenopropyl)-Gly-Ile-Val-OMe (halogen= Br and Cl) inhibit the cytopathic effect induced by HIV-1 in CEM cell cultures and the reverse transcriptase activity in cell culture supernatants. The corresponding unsaturated N-allyl precursor also displays an antiviral effect. The title compounds inhibit the cytopathic effect induced by HIV-1 in CEM cell cultures and the reverse transcriptase activity in cell culture supernatants, without inhibiting the pol-protease and RT in vitro.