Research Summary - The last challenge in our lab before it shut down in January 2007 was the synthesis of the C-glycoside (C-galcer) analog of a powerful immunostimulant O- glycoside (O-galcer), originally found in a sponge off the coast of Okinawa, shown below. The "replacement" of the -O-link most commonly found in glycosides by -C- is a popular idea because the -C- material would not be vulnerable to cleavage by enzymes called glycosidases which are ubiquitous in living systems. The corollary to the increased stability of C- compared to O-glycosides is that the Lewis base/ hydrogen-bond accepting character of the natural oxygen is now replaced by a non-polar, hydrophobic CH2.

We were successful in the preparation of C-galcer, and with our principal collaborator, Dr. Moriya Tsuji (ADARC) have shown that the C-glycoside is a far superior immunostimulant than the parent O-glycoside. Recent papers from other groups throughout the world have confirmed this powerful activity. Compounds of this class of C-glycosides are now in the early stages commercial development.

Selected publications

A Single Early Activation of Invariant NK T Cells Confers Long-Term Protection against Collagen-Induced Arthritis in a Ligand-Specific Manner. Ken Coppieters, Katrien Van Beneden, Peggy Jacques, Pieter Dewint, Ann Vervloet, Bert Vander Cruyssen, Serge Van Calenbergh, Guangwu Chen, Richard W. Franck, Gust Verbruggen, Dieter Deforce, Patrick Matthys, Moriya Tsuji, Pieter Rottiers, and Dirk Elewaut J Immunol 2007, 179 2300-2309.

Combined Natural Killer T-Cell–Based Immunotherapy Eradicates Established Tumors in Mice Michele W.L. Teng, Jennifer A. Westwood, Phillip K. Darcy, Janelle Sharkey Moriya Tsuji, Richard W. Franck, Steven A. Porcelli, Gurdyal S. Besra, Kazuyoshi Takeda, Hideo Yagita, Michael H. Kershaw and Mark J. Smyth, Cancer Research 2007, 67, 7495-7504

Glycolipid alpha-C-galactosylceramide is a distinct inducer of dendritic cell function during innate and adaptive immune responses of mice, Fujii S, Shimizu K, Hemmi H, Fukui M, Bonito AJ, Chen G, Franck RW, Tsuji M, Steinman RM. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 11252-7.

E and Z alpha-C-galactosylceramides by Julia-Lythgoe- Kocienski chemistry: a test of the receptor-binding model for glycolipid immunostimulants.Chen G, Chien M, Tsuji M, Franck RW. Chembiochem. 2006, 7, 1017-22.

The Ramberg-Backlund reaction for the synthesis of C- glycosides, C-linked-disaccharides and related compounds. Taylor RJ, McAllister GD, Franck RW. Carbohydr. Res. 2006, 341, 1298-311.

Alpha-C-Galactosylceramides: Synthesis and Immunology, Richard W. Franck and Moriya Tsuji, Acct. Chem. Res. 2006, 39, 692-701

Glycolipid-presentation to NKT cells differs in an organ-dependent fashion, John Schmieg, Guangli Yang, Richard W. Franck, Nico Van Rooijen, & Moriya Tsuji PNAS 2005, 102, 1127-1132.

The Ramberg-Bäcklund Way to C-Glycosides, Peter S. Belica, Alain Berthold, Nikki Charles, Guangwu Chen, Ajit Parhi, Paolo Pasetto, Jun Pu, Guangli Yang and Richard W. Franck ACS-Symposium Series #896 "Modern Synthetic Methodologies Toward Glycomimetics" René Roy, ed. 2005, 107-119.