Variation of pKa in the N-terminal tyrosine side chain in octapeptide analogs of tendamistat influences alpha-amylase inhibition.

Peptide analogs of tendamistat were synthesized and analyzed for alpha-amylase inhibitory activity. The pK(a) of the N-terminal tyrosine was modified by incorporation of ring-substituted analogs, which alters hydrogen bonding capacity. K(i) values ranging from 70 to 524 microM generally increased with increasing pK(a), indicating a necessity for H-bond donor ability.