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

A series of peptides containing N-(2,3-dihalopropyl)-glycine or alanin e residues has been prepared as potential suicide substrates of the HI V pol-protease or as enzyme-activated prodrugs. Halogenation of unsatu rated N-allyl peptide precursors in dichloromethane occurs with partic ipation of a neighboring amide group and leads to halohydrins instead of the expected dihalides. Use of X(2)/LiX/HOAc conditions gives the d esired dihalogenated derivatives. These fractionalized substrate analo gs are not inhibitors of the enzyme. However, Boc-Ala-Phe-N-(2,3-dihal ogenopropyl)-Gly-Ile-OMe (halogen= Br and Cl) inhibit the cytopathic e ffect induced by HIV-1 in CEM cell cultures and the reverse transcript ase activity in cell culture supernants. The corresponding unsaturated N-allyl precursor also displays an antiviral effect.