Glycoproteins are important protein conjugates. They are found mainly on the cell surface or in secretory form and exert many biological functions. In many cases the carbohydrate is influencing the activity of a glycoprotein. However, natural glycoproteins are mixtures of glycoforms, which cannot be separated in most cases. Thus total synthesis of homogeneous glycoproteins has become an attractive target.[1] Native chemical ligation has enabled the synthesis of entire proteins including those carrying posttranslational modifications.[2] We have integrated recombinant protein fragments for bovine ribonuclease[3] and human interleukin 6 into a semisynthetic approach. Due to synthetic limitations[4] multiple ligations of functionalized synthetic peptides and glycopeptides are required.[5] In order to expand this approach to the synthesis of libraries of glycoforms several new challenges need to be met. This includes the synthesis of the desired N-glycans and their convenient coupling to the peptide chains in a highly convergent manner.[6]
[1] a) D. P. Gamblin, E. M. Scanlan, B. G. Davis, Chem. Rev., 2009, 109, 131; b) C. Unverzagt, Y. Kajihara, Chem. Soc. Rev., 2013.
[2] P. E. Dawson, T. W. Muir, I. Clark-Lewis, S. B. Kent, Science, 1994, 266, 776.
[3] a) C. Piontek, P. Ring, O. Harjes, C. Heinlein, S. Mezzato, N. Lombana, C. Pöhner, Markus Püttner, D. Varón Silva, A. Martin, F. X. Schmid, C. Unverzagt, Angew. Chem. Int. Ed., 2009, 48, 1936; b) C. Piontek, D. Varón Silva, C. Heinlein, C. Pöhner, S. Mezzato, P. Ring, A. Martin, F. X. Schmid, C. Unverzagt, Angew. Chem. Int. Ed., 2009, 48, 1941.
[4] C. Heinlein, D. Varón Silva, A. Tröster, J. Schmidt, A. Gross, C. Unverzagt, Angew. Chem. Int. Ed. 2011, 50, 6406–6410.
[5] D. Bang and S. B. Kent, Angew. Chem. Int. Ed., 2004, 43, 2534.
[6] V. Ullmann, M. Rädisch, I. Boos, J. Freund, C. Pöhner, S. Schwarzinger, C. Unverzagt, Angew. Chem. Int. Ed. 2012, 51, 11566-11570.
