Unverzagt

Due to its medical importance erythropoietin (EPO) is one of the best-studied recombinant therapeutic glycoproteins. In seminal studies it was revealed that the function of erythropoietin is highly dependent on the presence and the structure of its carbohydrate moieties. Despite many efforts the isolation of
homogeneous EPO glycoforms is still not feasible and biological studies can only use mixtures of glycoforms. Thus, synthetic alternatives are desirable aiming at the generation of pure EPO glycoforms needed for more detailed structure-activity-relationships.

We have established a semisynthetic route to bioactive EPO with an Asn 24 N-glycan using a newly developed convergent synthesis for glycopeptides with all natural linkages. The glycan of Asn 24 can thus be varied readily in order to correlate systematically varied carbohydrate sstructures to the bioactivity of the protein, its intrinsic stability and the propensity to crystallize. A synthetic access to glycoforms of fully N- and O-glycosylated EPO will also be investigated. The systematic library of variants of natural glycoforms of EPO should provide general insights into the roles of carbohyddrates in glycoproteins and may guide the future engineering of glycoforms.

C.G.F. Graf, C. Schulz, M. Schmälzlein, C. Heinlein, M. Mönnich, L. Perkams, M. Püttner, I. Boos, M. Hessefort, J.N. Lombana Sanchez, M. Weyand,  C. Unverzagt
Angew. Chem. Int. Ed.2017, 56(19), 5252-5257
Synthetic Glycoforms reveal Carbohydrate-Dependent Bioactivity of Human Saposin D
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M. Mönnich, S. Eller, T. Karagiannis, L. Perkams, T. Luber, D. Ott, M. Niemietz, J. Hoffman, J. Walcher, L. Berger, M. Pischl, M. Weishaupt, C. Wirkner, R.G. Lichtenstein, C. Unverzagt
Angew. Chem. 2016, 128, 10643-10648
Angew. Chem. Int. Ed.2016, 55, 10487-10492
Highly Efficient Synthesis of Multiantennary Bisected N-glycans Based on Imidates
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A. Reif, S. Siebenhaar, A. Tröster, M. Schmälzlein, C. Lechner, P. Velisetty, K. Gottwald, C. Pöhner, I. Boos, V. Schubert, S. Rose-John, C. Unverzagt
Angew. Chem. 2014, 126, 12321-12327
Angew. Chem. Int. Ed. 2014, 53, 12125-12131
Semisynthesis of Biologically Active Glycoforms of the Human Cytokine Interleukin 6
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C. Pöhner, v. Ullmann, R. Hilpert, E. Samain, C. Unverzagt
Tetrahedron Lett. 2014, 55, 2197-2200
Chemoselective coupling of sugar oximes and α-ketoacids to glycosyl amides and N-glycopeptides
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C. Unverzagt, Y. Kajihara
Chem. Soc. Rev. 2013, 42, 4408-4420
Chemical assembly of N-glycoproteins: a refined toolbox to address a ubiquitous posttranslational modification
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V. Ullmann, M. Rädisch, I. Boos, J. Freund, C. Pöhner, S. Schwarzinger, C. Unverzagt
Angew. Chem. Int. Ed. 2012, 51, 11566-11570
Convergent Solid Phase Synthesis of N-Glycopeptides supported by Pseudoprolines at Consensus Ser/Thr Residues
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D. Ott, J. Seifert, I. Prahl, M. Niemietz, J. Hoffman, J. Guder, M. Mönnich, C. Unverzagt
Eur. J. Org. Chem. 2012, 26, 5054-5068
Modular Synthesis of Core Fucosylated N-Glycans
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