|Edwards, Judson - Vince|
Submitted to: Biomedical Materials Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/17/2013
Publication Date: 5/17/2013
Citation: Edwards, J.V., Caston-Pierre, S. 2013. Citrate-linkekd keto- and aldo-hexose monosaccharide cellulose conjugates demonstrate selective human neutrophil elastase-lowering activity in cotton dressings. Journal of Functional Biomaterials. 4:59-73. Interpretive Summary: This manuscript addresses a major worldwide health care problem involving the treatment of chronic wounds with new wound dressings designed to lower destructive levels of proteases found in non-healing wounds. The research reported in this paper outlines a route to attaching simple carbohydrates to cotton that act to enhance uptake of the destructive protease Elastase. The lowering of elastase would prevent breakdown of important growth factors that promote wound healing. The manuscript shows how to attach the carbohydrates to cotton and that the resulting products work differently based on their structure. For example, fructose attached to cotton lowers elastase activity better than glucose. This paper is an important contribution to understanding the structure function properties of simple carbohydrates attached to cotton, and may have application in the mechanism-based treatment of chronic wounds. It also provides a value-added cotton product that meets and unmet consumer need, and provides a route for better cotton utilization to further assist the cotton farmer.
Technical Abstract: Sequestration of harmful proteases from the chronic wound environment has become an important goal of wound dressing design and function. The protease human neutrophil elastase is a serine protease having electrophilic inhibitors that have been designed based on acylation by aldehyde and ketone functional groups of Serine-195 at the active site of the enzyme. We have probed the elastase-lowering activity of monosaccharide cellulose conjugates containing aldohexose and ketohexose with this mechanism of activity in mind. The monosaccharide-cellulose conjugates were prepared on cotton gauze as prototype wound dressing analogs and assayed for elastase-lowering activity. A series of four aldohexose and four ketohexose cellulose conjugates were synthesized on cotton gauze through a citric acid esterification reaction. The monosaccharide component of the cellulose conjugates was characterized by hydrolysis of the citrate ester of the monosaccharide and analysis of the monosaccharide with high performance anion exchange chromatography. The citrate-cellulose ester bonds were characterized with FTIR. Both ketohexose and aldohexose conjugate levels were quantified on cotton and found to be conjugated in low milligram/gram amounts. The relative elastase-lowering activities of both families of monosaccaride conjugates were also compared and the order of activity found to be ketohexose-citrate-cellulose conjugates > aldohexose-citrate-cellulose conjugates. Each family of the ketohexose and aldohexose conjugates gave dose response plots with initial rate profiles of the keto and aldo analogs. The ketohexose conjugates demonstrated greater activity in lowering elastase activity. A proposed mechanism of sequestration based on an enzyme active site pharmacophore model is correlated with enzyme subsite requirements for binding.