Biological antifreezes enable life in polar and subpolar waters at temperatures about -1.9 °C. One class of these is the antifreeze glycoprotein (AFGP), which is classified further into eight subtypes according to the covered mass fraction. It is little known about the molecular mechanism of antifreeze activity due to the tedious purification from natural sources and challenging synthesis of heavily glycosylated peptides. AFGP consist of a varying number of (Ala-Ala-Thr)n (n=4-55), whereas every threonine side chain is glycosylated with β-D-galactosyl-(1→3)-α-N-acetyl-D-galactosamine. This pattern is highly conserved among different species. Minor sequence variations where alanine is substituted by proline or the glycosylated threonine by arginine are biologically active. The proteins and peptides initiate thermal hysteresis, change the crystal habit and suppress recrystallization and heterogeneous ice nucleation. Although essential moieties of the peptides are known, the protein/peptide-ice interface is not yet understood. Particularly, the account of sequence variations has barely been elucidated.
Figure 1: Primary structure of AFGP.
The initial step is the preparation of a glycosylated threonine building block, which is further incorporated into solid phase peptide synthesis, what enables the preparation of AFGP analogs containing proline and other structure inducing amino acids for elucidation of structure activity relationships. The peptides are structurally analyzed by NMR, CD and FRET experiments. Furthermore, their activity is tested by in recrystallization assays.
The project is supported by the DFG (SFB 613).
Biocompatibility of technical surfaces: Protein Adsorption and Cell Adhesion, WWU Münster, 2008.
L. Nagel, C. M. Forsyth, L. L. Martin, Acta Cryst. 2007, E63, m2193.
L. Nagel, C. Plattner, C. Budke, Z. Majer, A. L. DeVries, T. Berkemeier, T. Koop, N. Sewald, Amino Acids 2011, 41(3), 719-732.
S. Bollmann, A. Burgert, C. Plattner, L. Nagel, N. Sewald, M. Löllmann, M. Sauer, & S. Doose, ChemPhysChem 2011, 12, 2907-2911.
L. Nagel, C. Budke, R. S. Erdmann, A. Dreyer, T. Koop, H. Wennemers, N. Sewald, Chem. Eur. J., accepted.
L. Nagel, C. Budke, A. Dreyer, T. Koop, N. Sewald, Beilstein J. Org. Chem., in preparation.
|Oct. 2010||“Living below the Freezing Point - Synthetic Antifreeze Glycopeptides”, Foldamers: Design, Synthesis & Applications, Bologna, Italy|
|Mar. 2010||“Microwave Assissted SPPS of PhoB-Peptides & AFGPs”, Peptide - Von der Synthese bis zur Analyse, Varian Deutschland GmbH und CEM GmbH, Kamp-Lintfort, Germany|
|Dec. 2009||“Synthesis of Antifreeze Glycopeptide Analogs”, University Eötvös Loránd, Budapest, Hungary|
|Mar. 2011||“Synthetic Antifreeze Glycopeptide Analogs”, 10th German Peptide Symposium, Berlin, Germany|
|Sep. 2010||“Synthetic Antifreeze Glycopeptide Analogs”, 31st European Peptide Symposium, Copenhagen, Denmark|
|Jan. 2010||“Synthetic Antifreeze Glycopeptide Analogs”, Foldamers: From design to protein recognition, Bordeaux, France|
|Mar. 2009||“Synthetic Antifreeze Glycopeptide Analogs”, 9th German Peptide Symposium, Göttingen, Germany|
|Apr. 2008||“Protein adsorption on technical surfaces”, International Workshop on Mechanical and Electrical Properties of artificial and cellular Membranes, Gomadingen, Germany|
Here you will find personal data and further information about the members of the workgroup Organic Chemistry III.
|Mrs. Iris Dopheide|
|Phone:||0521 106 6963|
|Fax:||0521 106 8094|