Synthesis and activity of NH2- and COOH-terminal elastase recognition sequences on cotton

The application of peptide recognition sequences of elastase to fibers of wound dressings is a possible route to inhibiting high levels of destructive elastase in the chronic wound. For this reason we have synthesized the elastase recognition sequence Val-Pro-Val on both cotton cellulose, and carboxymethylated cellulose cotton (CMC) and prepared chromatography columns of these to examine elastase retention. The tripepride was synthesized on cotton-based cellulose fibers both in sequence and as a tripeptide methyl ester. Glycine war employed as a linker of the recognition sequence to the cotton cellulose. Pretreatment of cotton cellulose with cellulase improved the substitution level of glycine. The peptidocellulose conjugates were employed asa chromatographic stationary phase to assess elastase retention. The sequence Val-Pro-Val-OMe was amino-terminally anchored to carboxymethylated cotton and demonstrated retention of up to 58% of elastase when first applied to the column. Higher repetitive retention was demonstrated subsequently. Cotton gauze similarly modified with Val-Pro-Val-Gly cellulose was compared with untreated gauze for reduction of elastase activity in buffered saline. Solutions of elastase that were treated with Val-Pro-Val-Gly cellulose cotton gauze, demonstrated reduced elastase activity. This study demonstrates the use of elastase recognition sequences as sequestering agents of elastase when attached to cotton fibers and constitutes a model far the design of peptidocellulose analogs in dressing fibers for chronic wounds.