Cyclic and linear peptides derived from alpha-amylase inhibitory protein tendamistat

Tendamistat is a strong inhibitory protein of porcine pancreatic alpha -amy lase (PPA) with a K-i value of 0.2 nM, To develop potent alpha -amylase inh ibitors, we synthesized six odd-length cyclic peptides (5-15 residues) and four even-length cyclic peptides (10 and 12 residues) having the inhibitory sequence of tendamistat, Their PPA inhibitory activities were evaluated, a nd, among them, the 11-residue cyclic peptide Ten(15-23) (K-i = 0.27 muM) e xhibited the strongest inhibitory activity (K-i = 0.27-1.41 muM). To examin e the effect of cyclic structure on PPA inhibition ten linear peptides corr esponding to the cyclic peptides were also synthesized, and their PPA inhib itory activities were evaluated (K-i = 0.28-1.00 muM). Interestingly, the 1 1-residue linear peptide Ten(15-23) exhibited almost the same inhibitory ac tivity (K-i = 0.28 muM) as that of cyclic Ten(15-23), The results of a circ ular dichroism study indicated that stabilization of the g-hairpin structur e occurred only for cyclic Ten(15-23), Also, the results of proteolytic dig estion experiments of the cyclic and linear Ten(15-23) peptides by trypsin and chymotrypsin suggested no differences in protease resistance between th e cyclic and linear structures. Therefore, we demonstrated that both cyclic and linear peptides containing the inhibitory sequence of tendamistat exhi bit potent PPA inhibitory activity.