2nd Generation C-glycoside analogues of KRN7000-Simplifying access to potent invariant Natural Killer T-Cell activators
Standing
Undergraduate
Type of Proposal
Oral Presentation
Faculty
Faculty of Science
Proposal
KRN 7000 was first isolated from a Japanese marine sponge over 20 years ago. This α-galactosylceramide activates the invariant Natural Killer T cell system and induces cytokine production, resulting in a systemic non-specific immune response. The molecule is not tolerant of structural variation, and one of the only active analogues is the C-glycoside where the anomeric oxygen is replaced with a methylene group, increasing the molecule’s stability in vivo. This analogue is approximately one hundred times more potent than natural KRN 7000, potentially making it a very suitable candidate for clinical application; however, the cost of the current synthesis makes this prohibitive. While many structural aspects of this C-glycoside have been explored, no one has attempted to modify the length of the linker between the sugar and the ceramide moieties. This might be tolerated, and more importantly, it would reduce the cost of the synthesis exponentially. In this presentation we will discuss our progress towards these new constructs.
Location
University of Windsor
Grand Challenges
Sustainable Industry
2nd Generation C-glycoside analogues of KRN7000-Simplifying access to potent invariant Natural Killer T-Cell activators
University of Windsor
KRN 7000 was first isolated from a Japanese marine sponge over 20 years ago. This α-galactosylceramide activates the invariant Natural Killer T cell system and induces cytokine production, resulting in a systemic non-specific immune response. The molecule is not tolerant of structural variation, and one of the only active analogues is the C-glycoside where the anomeric oxygen is replaced with a methylene group, increasing the molecule’s stability in vivo. This analogue is approximately one hundred times more potent than natural KRN 7000, potentially making it a very suitable candidate for clinical application; however, the cost of the current synthesis makes this prohibitive. While many structural aspects of this C-glycoside have been explored, no one has attempted to modify the length of the linker between the sugar and the ceramide moieties. This might be tolerated, and more importantly, it would reduce the cost of the synthesis exponentially. In this presentation we will discuss our progress towards these new constructs.