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Project P7: Heteromultivalent Glycomacromolecules as Sensors and Inhibitors of Viral Interactions

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Precision glycomacromolecules are a novel class of polymeric glycan mimetics comprised of a monodisperse, sequence-controlled oligo(amidoamine) scaffold with glycan side chains. They are synthesized through iterative assembly on solid support using tailor made building blocks, followed by subsequent site-selective installation of functionalized glycans using different conjugation methods. In the previous funding period, we introduced a series of homo- and heterovalent glycomacromolecules targeting non-enveloped viruses and together with our collaboration partners in the consortium began analyzing their binding and inhibitor properties showing promising results. Based on these findings we now plan to further extend our library of glycomacromolecules to include non-glycan fragments as well as site-selectively sulfated glycans. Furthermore, glycomacromolecules will be used as macromolecular building blocks in a bottom-up approach towards glycofunctionalized membranes and surfaces giving access to highly functional yet highly controlled particles to investigate the effects of surface-presentation on viral adhesion and potentially derive novel inhibitors thereof.

Figure: Exemplary glycomacromolecule for the bottom-up design of glycofunctionalized materials such as nanoparticles, liposomes, microgels and surfaces.



Soria-Martinez, L.; Bauer, S.; Giesler, M.; Schelhaas, S.; Materlik, J.; Janus, K.; Pierzyna, P.; Becker, M.; Snyder, N. L.; Hartmann, L; Schelhaas, M, “Prophylactic Antiviral Activity of Sulfated Glycomimetic Oligomers and Polymers”. Journal of the American Chemical Society. 2020142, 5252-5265. Link

Baier, M.; Rustmeier, N. H.; Harr, J.; Cyrus, N.; Reiss, G. J.; Grafmüller, A.; Blaum, B. S.; Stehle, T.; Hartmann, L., "Divalent Sialylated Precision Glycooligomers Binding to Polyomaviruses and the Effect of Different Linkers". Macromolecular Bioscience. 2019, 19, 1800426. Link

Bücher, K. S.; Konietzny, P. B.; Snyder, N. L.; Hartmann, L., "Heteromultivalent Glycooligomers as Mimetics of Blood Group Antigens". Chemistry – A European Journal. 2019, 25, 1 -10. Link

Baier, M.; Ruppertz, J. L.; Pfleiderer, M. M.; Blaum, B. S.; Hartmann, L., Synthesis of highly controlled carbohydrate–polymer based hybrid structures by combining heparin fragments and sialic acid derivatives, and solid phase polymer synthesis. Chemical Communications. 2018, 54, 10487-10490. Link

Bücher, K. S.; Yan, H.; Creutznacher, R.; Ruoff, K.; Mallagaray, A.; Grafmüller, A.; Dirks, J. S.; Kilic, T.; Weickert, S.; Rubailo, A.; Drescher, M.; Schmidt, S.; Hansman, G.; Peters, T.; Uetrecht, C.; Hartmann, L., Fucose-Functionalized Precision Glycomacromolecules Targeting Human Norovirus Capsid Protein. Biomacromolecules. 2018, 19, 3714-3724. Link

Bücher, K. S.; Babic, N.; Freichel, T.; Kovacic, F.; Hartmann, L., "Monodisperse Sequence-Controlled α-l-Fucosylated Glycooligomers and Their Multivalent Inhibitory Effects on LecB". Macromolecular Bioscience. 2018, 18, 1800337. Link

Stehle, T.; Peters, T.; Hartmann, L.; Schelhaas, M., Glycans Controlling Virus Infections: Meeting Report on the 1st International Symposium on Glycovirology Schöntal, Germany, 02–04 May 2018. Viruses 2018, 10(11), 636. Link

M. Baier, M. Giessler, L. Hartmann, Split & Combine Approach towards Branched Precision Glycomacromolecules and their Lectin Binding Behavior, Chemistry – A European Journal, 2018, 24(7), 1619-1630. Link