Sub‐site preferences of the aspartic proteinase from the human immunodeficiency virus, HIV‐1

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Abstract
A series of synthetic, chromogenic substrates for HIV‐1 proteinase with the general structure Ala‐Thr‐His‐Xaa‐Yaa‐Zaa∗Nph‐Val‐Arg‐Lys‐Ala was synthesised with a variety of residues introduced into the Xaa, Yaa and Zaa positions. Kinetics parameters for hydrolysis of each peptide by HIV‐1 proteinase at pH 4.7, 37°C and u = 1.0 M were measured spectrophotometrically and/or by reverse phase FPLC. A variety of residues was found to be acceptable in the P3, position whilst hydrophobic/aromatic residues were preferable in P1. The nature of the residue occupying the P2; position had a strong influence on k cat (with little effect on k m;β‐branched residues Val or Ile in this position resulted in considerably faster peptide hydrolysis than when e.g. the Leu‐containing analogue was present in P2.