DELINEATING FUNCTIONALLY IMPORTANT REGIONS AND RESIDUES IN THE CATHEPSIN-B PROPEPTIDE FOR INHIBITORY ACTIVITY

Synthetic peptides derived from the proregion of rat cathepsin B were used to identify functionally important regions and residues for cathe psin B inhibition. Successive 5 amino acid deletions of a 56 amino aci d propeptide from both the N- and C-termini has allowed the identifica tion of two regions important for inhibitory activity: the NTTWQ (resi dues 21p-25p) and CGTVL (42p-46p) regions, Alanine scanning of residue s within these two regions indicates that Trp-24p and Cys-42p contribu te strongly to inhibition, their replacement by Ala resulting in 160- and 140-fold increases in K-i, respectively.