Satoshi Tsuboi

Significant effects of Z-Gln-Val-Val-OMe, common sequences of thiol proteinase inhibitors on thiol proteinases

The first studies on a series of the small synthetic thiol proteinase inhibitors, conservative common sequences in several thiol proteinase inhibitors, are described. Among the many interesting findings with synthetic thiol proteinase inhibitors was the observation that the most effective analogue, Z-Gln-Val-Val-Ala-Gly-OMe, whose amino and carboxyl groups were protected with Z and OMe, respectively, showed inhibitory activity on papain and cathepsin B and protected papain from egg cystatin, human low-molecular-weight kininogen and T-kininogen-induced inhibition but not from leupeptin-induced inhibition. Moreover, it was revealed that Z-Gln-Val-Val-OMe was the smallest peptide to exhibit a protective effect on papain.

Synthesis of peptide fragments related to eglin c and examination of their inhibitory effect on human leukocyte elastase, cathepsin G and α-chymotrypsin

Various kinds of peptide fragments related to eglin c were prepared by the conventional solution method and their inhibitory effects on human leukocyte elastase, cathepsin G and alpha-chymotrypsin were examined. Peptide (31-40) inhibited cathepsin G (Ki = 2.3 x 10(-4) M), peptide (41-49) potently inhibited cathepsin G and alpha-chymotrypsin (Ki = 4.2 x 10(-5) M and 2.0 x 10(-5) M, respectively), and peptide (60-63) inhibited leukocyte elastase (Ki = 1.6 x 10(-4) M), whereas, peptide (31-35) weakly inhibited both elastase and cathepsin G (Ki = 2.1 x 10(-3) M and 7.3 x 10(-4) M, respectively).

Synthesis of a trihexacontapeptide corresponding to the sequence 8–70 of eglin c and studies on the relationship between the structure and the inhibitory activity against human leukocyte elastase, cathepsin G and α-chymotrypsin

A trihexacontapeptide corresponding to the sequence 8–70 of eglin c and its related peptides were synthesized by the conventional solution method and their inhibitory activity against human leukocyte elastase, cathepsin G and α‐chymotrypsin was examined. Although synthetic eglin c (41–49) inhibited cathepsin G and α‐chymotrypsin (K i = 4.0 × 10−5 M and 2.0 × 10−5 M, respectively) but not leukocyte elastase, the synthetic trihexaconta‐peptide potently inhibited cathepsin G, α‐chymotrypsin and leukocyte elastase (K i = 1.8 × 10−9 M, 1.4 × 10−9 M and 2.2 × 10−9 M, respectively). The relationship between the stucture of eglin c and the inhibitory activity against the above enzymes is also described.