a b s t r a c t Novel linear and cyclic glycotetrapeptides were designed, synthesized and tested for inhibition of the wild type C-SA HIV-1 protease enzyme. The incorporation of b-amino acid sugar to the linear and cyclic peptides resulted in a series of fifteen novel compounds. Linear glycopeptide 4a and cyclic glycopeptide 6a displayed significant activities against the HIV protease enzyme. The experimental results were compared with a computational approach using molecular docking. The sugar hydroxyl group at the C 3 position in linear (4a) as well as cyclic glycopeptide (6a), shows hydrogen bonding interaction with the enzymatic Asp25/Asp25 0 residues in docking studies. Ó 2012 Elsevier Masson SAS. All rights reserved.