Synthesis of Novel Arginine Building Blocks with Increased Lipophilicity Compatible with Solid-Phase Peptide Synthesis.

Arginine, due to the guanidine moiety, increases peptides' hydrophilicity and enables interactions with charged molecules, but at the same time, its presence in a peptide chain might reduce its permeability through biological membranes. This might be resolved by temporary coverage of the peptide charge by lipophilic, enzyme-sensitive alkoxycarbonyl groups. Unfortunately, such a modification of a guanidine moiety has not been reported to date and turned out to be challenging.

Truncation of Huia versabilis Bowman-Birk inhibitor increases its selectivity, matriptase-1 inhibitory activity and proteolytic stability.

A gradual truncation of the primary structure of frog skin-derived Huia versabilis Bowman-Birk peptidic inhibitor (HV-BBI) resulted in 18-times stronger inhibitor of matriptase-1 (peptide 6, K = 8 nm) in comparison to the full-length HV-BBI (K = 155 nm). Analogous increase in the inhibitory activity in correlation with the peptide length reduction was not observed in case of other serine proteases, bovine trypsin (K = 151 nm for peptide 6 and K = 120 nm for HV-BBI) and plasmin (K = 120 nm for peptide 6 and 82 nm for HV-BBI). Weaker binding affinity to these enzymes emphasized an inhibitory specificity of peptide 6.