F Lecaille, J Cotton, J H McKerrow, M Ferrer-Di Martino, E Boll-Bataillé, F Gauthier, G Lalmanach
Laboratoire d"Enzymologie et Chimie des Protéines, INSERM EMI-U 0010, Université Francois Rabelais, Faculté de Médecine, Tours, France.
FEBS letters 2001 Nov 2A library of 121 pseudopeptides was designed to develop reversible inhibitors of trypanosomal enzymes (cruzain from Trypanosoma cruzi and congopain from Trypanosoma congolense). The peptides share the framework: Cha-X1-X2-Pro (Cha=cyclohexyl-alanine, X1 and X2 were phenylalanyl analogs), based on a previous report [Lecaille, F., Authié, E., Moreau, T., Serveau, C., Gauthier, F. and Lalmanach, G. (2001) Eur. J. Biochem. 268, 2733-2741]. Five peptides containing a nitro-substituted aromatic residue (Tyr/Phe) and one a 4-chloro-phenylalanine at the X1 position, and 3-(2-naphthyl)-alanine, homocyclohexylalanine or 3-nitro-tyrosine (3-NO(2)-Tyr) at the X2 position, were selected. They inhibited congopain more effectively than cruzain, except Cha-4-NO(2)-Phe-3-NO(2)-Tyr-Pro which bound the two parasitic enzymes similarly. Among this series, Cha-3-NO(2)-Tyr-HoCha-Pro and Cha-4-NO(2)-Phe-3-NO(2)-Tyr-Pro are the most selective for congopain relative to host cathepsins. No hydrolysis occurred upon prolonged incubation time with purified enzymes. In addition introduction of non-proteogenic residues in the peptidyl backbone greatly enhanced resistance to proteolysis by mammalian sera.
F Lecaille, J Cotton, J H McKerrow, M Ferrer-Di Martino, E Boll-Bataillé, F Gauthier, G Lalmanach. Reversible inhibition of cathepsin L-like proteases by 4-mer pseudopeptides. FEBS letters. 2001 Nov 2;507(3):362-6
PMID: 11696372
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