Department of Chemistry Seminar Announcement

1. Department of Chemistry Seminar Announcement About the Speaker Professor Peter H. Seeberger received his Vordiplom in 1989 from the Universität Erlangen-Nürnberg. In 1995 he earned his Ph.D. from the University of Colorado. After a postdoctoral fellowship at the Sloan-Kettering Institute for Cancer Research in New York, he became Assistant Professor at the Massachusetts Institute of Technology in January 1998 and was promoted to Firmenich Associate Professor of Chemistry in 2002. From June 2003 until January 2009, he held the position of Professor for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zurich. In 2009, he assumed position as Director at the Max-Planck Institute for Colloids and Surfaces in Potsdam and Professor at the Free University of Berlin. He serves as an Affiliate Professor at the Sanford-Burnham Institute in La Jolla, CA. Prof Seeberger was awarded the Tetrahedron Young Investigator Award 2010 for Bioorganic and Medicinal Chemistry. Abstract Most pathogens including bacteria, fungi, viruses and protozoa carry unique glycans on their surface. Currently, three vaccines against H. influenza type B (Hib), S. pneumoniae (Prevnar) and N. meningitides (Menactra) are being marketed. All three carbohydrate conjugate vaccines are based on isolated polysaccharides. Since many pathogens cannot be cultured and the isolation of pure oligosaccharides is extremely difficult, synthetic oligosaccharide antigens provide now a viable alternative. Based on the automated synthesis platform,1 the MPI department together with Ancora Pharmaceuticals (Medford, USA) is currently developing multiple vaccine candidates against hospital-acquired bacterial infections, fungi, and protozoan parasites. This lecture will use B. anthracis2,3 as an example to demonstrate the approach. The development of a vaccine against malaria will be illustrated in more detail, particularly molecular insights into the infection mechanism.4Plasmodium falciparum, the most deadly form of the protozoan parasite that causes malaria, enters human erythrocytes as part of its complex life cycle. We have shown that glycosyl phosphatidyl inositol (GPI) glycans, present on the surface of merozoites, interact with a protein on the surface of the host cell. Targeting the GPI-moesin recognition process should enable novel modes of therapeutic intervention and vaccination against malaria. We present a versatile screening method based on microarrays of synthetic glycans that differentiates between malaria dependent and malaria independent adaptive immune responses to GPI.5 1. Plante, O.J.; Palmacci, E.R.; Seeberger, P.H.; Science2001, 291, 1523. 2. Tamborrini, M.; Werz, D. B.; Frey, J.; Pluschke, G.; Seeberger, P.H.; Angew. Chem. Int. Ed.2006, 45, 6581. 3. Oberli, M.A.; Tamborrini, M.; Tsai, Y.-H.; Werz, D.B.; Horlacher, T.; Adibekian, A.; Gauss, D.; Möller, H.M.; Pluschke, G.; Seeberger, P.H.; J. Am.Chem. Soc.2010, 132, 10239-10241. 4. Schofield, L.; Hewitt, M.C.; Evans, K.; Siomos, M.A.; Seeberger, P.H.; Nature, 2002, 418, 785. 5. Kamena, F.; Tamborrini, M.; Liu, X.; Kwon, Y.-U.; Thompson, F.; Pluschke, G.; Seeberger; P.H.; Nature Chem. Bio., 2008, 4, 238. All are Welcome

2. Department of Chemistry Seminar Announcement About the Speaker Professor Peter H. Seeberger received his Vordiplom in 1989 from the Universität Erlangen-Nürnberg. In 1995 he earned his Ph.D. from the University of Colorado. After a postdoctoral fellowship at the Sloan-Kettering Institute for Cancer Research in New York, he became Assistant Professor at the Massachusetts Institute of Technology in January 1998 and was promoted to Firmenich Associate Professor of Chemistry in 2002. From June 2003 until January 2009, he held the position of Professor for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zurich. In 2009, he assumed position as Director at the Max-Planck Institute for Colloids and Surfaces in Potsdam and Professor at the Free University of Berlin. He serves as an Affiliate Professor at the Sanford-Burnham Institute in La Jolla, CA. Prof Seeberger was awarded the Tetrahedron Young Investigator Award 2010 for Bioorganic and Medicinal Chemistry. Abstract Carbohydrates in form of glycoconjugates decorate the surface of cells and are key to many important biological recognition events. The placement of well-defined, synthetic glycans on surfaces can be used for delivery, molecular imaging and sensing applications. Described is a host of nanostructures equipped with synthetic cell-surface carbohydrates. Nanoparticles,1 surfaces,2 metallo-dendrimers3 and supramolecular assemblies4 not only possess interesting structural but also electrochemical and fluorescent properties. These novel structures were applied to diagnostic and imaging applications in vitro and in vivo. Reported are also molecular logic operations using such nanostructures.5 In addition, the use of continuous flow reactors to produce large quantities of nanoparticles will be discussed. 6 Kikkeri, R.; Lepenies, B.; Adibekian, A.; Laurino, P.; Seeberger, P.H.; In Vitro Imaging and In Vivo Liver Targeting with Carbohydrate Capped Quantum Dots; J. Am.Chem. Soc.2009, 131, 2110. Kikkeri, R.; Gupta, T.; Hossain, L.H.; Kamena, F.; Gorodyska, G.; Beurer, E.; Textor, M.; Seeberger, P.H.; Ru(II)-Glycodendrimers as Probes to Study Lectin-Carbohydrate Interactions and Electrochemically Measure Mono- and Oligosaccharide Concentrations; Langmuir 2010, 26, 1520. a) Kikkeri, R.; Hossain, L.H.; Seeberger, P.H.; Supramolecular One-pot Approach to Fluorescent Glycodendrimers; Chem. Comm.2008, 2127 - 2129.b) Kikkeri, R.; García-Rubio, I.; Seeberger, P.H.; Ru(II)-Carbohydrate Dendrimers as Photoinduced Electron Transfer Lectin Biosensors; Chem. Comm.2009, 235. Kikkeri, R.; Grünstein, D.; Seeberger, P.H. in preparation. Kikkeri, R.; Grünstein, D.; Seeberger, P.H.; Lectin Biosensing Using Digital Analysis of Ru(II)-Glycodendrimers; J. Am.Chem. Soc.2010, 132, 10230. Kikkeri, R.; Laurino, P.; Odedra, A.; Seeberger, P.H.; Microreactor Synthesis of Carbohydrate Functionalized Quantum Dots; Angew. Chem. Int. Ed.2010, 49, 2054. Laurino, P.; Kikkeri, R.; Seeberger, P.H.; Continuous Flow Synthesis of Carbohydrate Capped Quantum Dots; Nature Protocols, 2011, in press. All are Welcome

3. Department of Chemistry Seminar Announcement About the Speaker Professor Peter H. Seeberger received his Vordiplom in 1989 from the Universität Erlangen-Nürnberg. In 1995 he earned his Ph.D. from the University of Colorado. After a postdoctoral fellowship at the Sloan-Kettering Institute for Cancer Research in New York, he became Assistant Professor at the Massachusetts Institute of Technology in January 1998 and was promoted to Firmenich Associate Professor of Chemistry in 2002. From June 2003 until January 2009, he held the position of Professor for Organic Chemistry at the Swiss Federal Institute of Technology (ETH) in Zurich. In 2009, he assumed position as Director at the Max-Planck Institute for Colloids and Surfaces in Potsdam and Professor at the Free University of Berlin. He serves as an Affiliate Professor at the Sanford-Burnham Institute in La Jolla, CA. Prof Seeberger was awarded the Tetrahedron Young Investigator Award 2010 for Bioorganic and Medicinal Chemistry. Abstract Traditionally, organic chemists have performed reactions in a batch-wise mode. In recent years continuous flow systems have become increasingly interesting to practitioners of synthetic chemistry. Described is the use of different micro- and meso-scale reactor systems to optimize reactions conditions, to carry out reactions otherwise too dangerous, or impossible to carry out on large scale. Amongst other examples, glycosylations, beta-peptide syntheses, organocatalysis and heterogeneous catalysis will be discussed. A particular focus will be placed on the preparation of nanoparticles and polymerizatons. Ratner, D.M., Murphy, E.R.; Jhunjhunwala, M.; Snyder, D.A; Jensen, K.F.; Seeberger, P.H.; Microreactor-based Reaction Optimization in Organic Chemistry; Chem. Comm. 2005, 578. Flögel, O.; Codée, J.D.C.; Murphy, E.R.; Jensen, K.F.; Seebach, D.; Seeberger, P.H.; Synthesis of a Poorly Soluble β-Peptide in a Microreactor; Angew. Chem. Int. Ed. 2006, 45, 7000. Geyer, K.; Codee, J.D.C.; Seeberger, P.H.; Microreactors as Tools for Synthetic Chemists – The Chemists’ Round-Bottom Flask of the 21st Century?; Chem. Eur. J. 2006, 12, 8434. Gustafsson, T.; Pontén, F.; Seeberger, P.H.; Trimethylaluminum Mediated Amide Bond Formation in a Continuous Flow Microreactor as Key to the Synthesis ofRimonabant and Efaproxiral; Chem. Comm. 2008, 1100. Gustafsson, T.; Gilmour, R.; Seeberger, P.H.; Fluorination Reactions in Microreactors; Chem. Comm. 2008, 3022. Odedra, A.; Seeberger, P.H.; 5-(Pyrrolidine-2-yl)tetrazole Catalyzed Aldol and Mannich Reactions: Acceleration and Lower Catalyst Loading in a Continuous-flow Reactor; Angew. Chem. Int. Ed. 2009, 48, 2699. Kikkeri, R.; Laurino, P.; Odedra, A.; Seeberger, P.H.; Microreactor Synthesis of Carbohydrate Functionalized Quantum Dots; Angew. Chem. Int. Ed. 2010, 49, 2054. Diehl, C.; Laurino, P.; Seeberger, P.H.; Accelerated Continuous Flow RAFT Polymerization; Macromolecules 2011, 44, in press. O’Brien, A.G.; Lévesque, F.; Seeberger, P.H.; Continuous flow thermolysis of azidoacrylates for the synthesis of heterocycles and pharmaceutical intermediates; Chem Comm, 2011, 47, in press. All are Welcome