The synthetic application of endohexosaminidase enzymes (e.g. Endo A, Endo M, Endo D) promises to allow ready access to a wide variety of defined homogenous glycoproteins and glycopeptides. In particular the use of N-glycan oligosaccharides that are activated at the reducing terminus as oxazolines [1] allows their high yielding attachment to almost any amino acid, peptide or protein that contains a GlcNAc residue as an acceptor. A wide variety of oxazoline donors are readily available, either by total synthesis [2] or by isolation of the corresponding oligosaccharide from natural sources and then conversion to the oxazoline in water.[3] Finally the synthetic potential of the enzymes is particularly augmented by the production of mutant glycosynthases.[4] The development of this methodology, and its application for the synthesis of a variety of defined glycopeptides of biological interest, including vaccine candidates and anti-diabetic agents, will be discussed.
References
1. Fujita, M.; Shoda, S.-I.; Haneda, K.; Inazu, T.; Takegawa, K.; Yamamoto, K.: Biochim. Biophys. Acta 2001, 1528, 9-14.
2. Rising, T. W. D. F.; Heidecke, C. D.; Moir, J. W. B.; Ling, Z.; Fairbanks, A. J.: Chem. Eur. J. 2008, 14, 6444-6464.
3. Noguchi, N.; Tanaka, T.; Gyakushi, H.; Kobayashi, A.; Shoda, S.-I.: J. Org. Chem. 2009, 74, 2210-2212
4. Heidecke, C.D.; Ling, Z.; Bruce, N. C.; Moir, J. W. B.; Parsons, T. B.; Fairbanks, A. J.: ChemBioChem 2008, 9, 2045-2051.
Contact local IBMM : Dr. Béatrice Roy