Grant: Strategic Projects - Group

Glucosamine (GlcN) is used extensively as an ""over the counter"" preparation for joint and bone disorders. However, it is not clear from clinical trials that it actually works. The main source GlcN is chitosan, which is derived from chitin, the most abundant polymer in the animal kingdom. So GlcN is a ""nutraceutical"". We have developed a series N-acylated glucosamines (GlcNAcyls), which are chemically modified nutriceuticals, for veterinary and human applications, primarily in arthritis and osteoporosis. Our preferred (lead) compound, N-butyryl glucosamine (GlcNBu) has shown positive effects in animal models for these applications, GlcN itself has not. Other applications, for which we have preliminary data, include enhancing animal growth and weight gain and possibly cognition and increased mobility in aged dogs. GlcNBu appears to have very little, if any, toxicity. Patents for the above applications have been issued in conjunction with the Canadian Arthritis Network, which is a National Centre of Excellence. Initially we will extend our studies on the mammalian applications. We will then study the possible mechanisms of action of GlcNBu and other GlcNAcs to account for the effects we see in animals. We will also investigate biological synthetic approaches, involving an important intermediary compound called butyryl Co-enzyme A, exists in mammals as well as in bacteria and algae. We will focus on the bacteria and common algae, since butyrly Co-enzyme A is known to be important in some types of bacteria and probably algae. Ultimately, we anticipate being able to apply biologic ""green technologies"" for the commercial synthesis of GlcNAcyls, utilizing bacterial or algae factories. Algae would be particularly attractive as they easily grow in water. Production of GlcNAcyls by bacteria or algae could have significant postive effects for the Canadian economy. Canadian supporting organizations include: CanCog (Toronto), Bioniche (Belleville) and Kingfisher International Inc (Stouffville). The project will train a signifcant number of Highly qualified personnel,