A simple method for semi-synthesis of peptidyl argininals as potent inhibitors of trypsin-like proteases.

Abstract

A simple method was developed for the conversion of leupeptin (acetyl-Leu-Leu-argininal) to other peptidyl argininals. Argininal dibutylacetal, a key intermediate, was produced by enzymatic digestion of leupeptin dibutylacetal with Pronase E and was isolated by column chromatography on CM-52 cellulose. N.alpha.-Blocked peptides (or amino acids) were connected to the .alpha.-amino group of this intermediate by conventional methods, and finally the acetal protecting group was removed by mild acid treatment to recover the essential aldehyde function. This novel method is applicable to large-scale preparation of many kinds of peptidyl argininals, which are promising candidates as specific inhibitors of trypsin-family proteases.