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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Synthetic Antifreeze Glycopeptide AnalogsLilly Nagel 1 , Carolin Plattner 1 , Carsten Budke 2 , Zsuzsa Majer 3 ,Thomas Koop 3 , and Norbert Sewald 11 Bielefeld University, Bielefeld, 33615, Germany; 2 Department of Physical Chemistry,Bielefeld University, Bielefeld, 33615, Germany; 3 Eötvös Loránd University,Budapest, 1518, HungaryIntroductionAntifreeze Glycopeptides (AFGP) are biological antifreezes in creatures living in polar andsubpolar areas. These proteins decrease thefreezing point of physiological fluids withoutchanges in melting point by inhibiting the growthof large ice crystals and suppressing heterogeneousice nucleation. Those polymers consist of iterativeFig. 1. Composition of AFGPs withimportant functionalities of antifreezeactivity.tripeptide units (Ala-Ala-Thr) n (n=4-56), whereevery threonine is linked to β-D-Galactosyl-(1→3)-α-N-acetyl-D-galactosamine (Figure 1), and adopthighly flexible threefold left-handed helices similarto the polyproline type II helix [1].Results and DiscussionSynthesis of the Building BlockSince AFGPs are not easily accessible from natural sources, the synthesis of such heavilyglycosylated peptides is necessary. Therefore, thesynthesis of glycosylated amino acid furnishedeither with a mono- or a disaccharide has to bedeveloped first before the building blocks areintroduced into peptide synthesis on solid phase.Both precursors of the T N - and T-antigens (Figure2) were obtained in a silver salts mediatedglycosylation. The carbohydrate could be coupledto the sidechain of a Fmoc-protected threoninegiving predominantly the α-anomeric product.Synthesis of PeptidesFig. 2. T N -antigen and T-antigenprecursors for solid phase peptidesynthesis.For the synthesis of these AFGP analogs, well-controlled and highly efficient couplingconditions during Fmoc-SPPS are essential. A semi-automated and microwave enhancedFig. 3. Microwave-enhanced synthesis of proline containing AFGP analogs on solid phase.86