Two series of peptidomimetics containing an N-hydroxyamino acid core structure were prepared by mixed solution solid-phase synthesis and tested for inhibitory activity against the human immunodeficiency virus (HIV-1) protease (Pr) and the virus in cell culture. In general, N-hydroxy Gly containing pseudopeptides displayed modest HIV Pr inhibition (IC50≥930 nM). In the N-hydroxy Phe derivatives, Fmoc-Phe-ψ[(CO-N OH)]-Phe-Pro-NHtBu was the best inhibitor of the series IC50 = 144nM showing satisfactory inhibition of HIV replication in cell culture (ED50 = 98 nM) and remarkable stability against cell culture and plasma enzymes.
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Financial support of this work by University of Ferrara and by Ministero dell'Università e della Ricerca Scientifica e Tecnologica (MURST) is gratefully acknowledged.