ANTI-HIV ACTIVITY OF N-(2,3-DIHALOGENOPROPYL)- AND N-ALLYL-GLYCINE CONTAINING PENTAPEPTIDES

Abstract 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.