Synthese monodisperser, multifunktionaler Neoglycopolymere und Neoglycopolymer-Hybride und ihre Anwendung in der Medizin
Final Report Abstract
In summary, we have established the solid phase polymer synthesis of monodisperse, sequence-defined glycooligo and –polymers or so-called precision glycomacromolecules. A library of functional building blocks in combination with optimized coupling conditions allows for the straightforward variation e.g. of the number and distance of side chains or the architecture of the backbone (linear, branched, cyclic). Using this synthetic platform, we have synthesized several sets of biomimetic polymers and glycopolymers. Major focus was devoted to the synthesis of glycooligo-/polymers as mimetics of natural multivalent sugar ligands. Specifically, we investigated the influence of the number and distance of sugar ligands attached to a precision scaffold, the influence of the scaffolds architecture and chemical properties as well the combination of different sugar ligands within one glycopolymer ligand. These glycopolymer ligands were then tested for a variety of potential biomedical applications such as their use as inhibitors for bacterial adhesion, antigen presenting platform in vaccine development and targeted delivery. Additionally we have developed a novel class of peptidomimetic polymers based on the same concept of solid phase polymer synthesis showing controlled secondary structure formation, highly increased proteolytic stability and a great potential as novel antibacterial therapeutic agents. The combination of our sequence-defined polymers with advanced hydrogel systems allows for a variety of biotechnological applications. Specifically, we developed a novel affinity assay based on sugar-ligand functionalized soft hydrogel particles. Furthermore, we were able to create biologically active hydrogel materials e.g. for the efficient catch and release of bacteria in solution. Overall, the results obtained in this study allowed for a deeper understanding of multivalent effects of polymeric ligands and will further promote potential applications of polymeric materials in biomedicine and biotechnology. Within the Emmy Noether project we could show the great variability of solid phase polymer synthesis and its usefulness for various areas of research from material sciences to biomedicine. Therefore future studies will extent the concept of solid phase synthesis also to other material classes beyond oligo- /polyamides and further promote the synthesis and application of precision polymers.
Publications
- Sequence-Defined Glycopolymer Segments Presenting Mannose: Synthesis and Lectin Binding Affinity, Biomacromolecules, 2012, 13, 1845-1852
D. Ponader, F. Wojcik, F. Beceren-Braun, J. Dernedde, L. Hartmann
(See online at https://doi.org/10.1021/bm300331z) - Solid-Phase Synthesis of Asymmetrically Branched Sequence- Defined Poly/Oligo(amidoamines) , J. Org. Chem., 2012, 77, 4226-4234
F. Wojcik, S. Mosca, L. Hartmann
(See online at https://doi.org/10.1021/jo202561k) - Synthesis and functionalization of poly(ethylene glycol) microparticles as soft colloidal probes for adhesion energy measurements, Soft Matter 2012, 8, 1664-1672
D. Pussak, M. Behra, S. Schmidt, L. Hartmann
(See online at https://doi.org/10.1039/c2sm06911c) - Magnetic Porous Sugar- Functionalized PEG Microgels for Efficient Isolation and Removal of Bacteria from Solution, Biomacromolecules, 2013, 14, 1927-1935
M. Behra, N. Azzouz, S. Mosca, M. Chanana, P. H. Seeberger, L. Hartmann
(See online at https://doi.org/10.1021/bm400301v) - Mechanical Carbohydrate Sensors based on Soft Hydrogel Particles, Angew. Chem. Int. Ed., 2013, 52, 6084-6087
D. Pussak, D. Ponader, S. Mosca, S. Vargas Ruiz, L. Hartmann and S. Schmidt
(See online at https://doi.org/10.1002/anie.201300469) - Synthesis of Carbohydrate-Functionalised Sequence-Defined Oligo(amidoamine)s by Photochemical Thiol-Ene Coupling in a Continous Flow Reactor, Chem. Eur. J., 2013, 19, 3090-3098
F. Wojcik, A. G. O'Brien, S. Götze, P. H. Seeberger and L. Hartmann
(See online at https://doi.org/10.1002/chem.201203927) - Synthesis of Homo- and Heteromultivalent Carbohydrate-Functionalized Oligo(amidoamines) Using Novel Glyco-Building Blocks, Beilstein J. Org. Chem., 2013, 9, 2395–2403
F. Wojcik,S. Lel,A. G. O’Brien, P. H. Seeberger and L. Hartmann
(See online at https://doi.org/10.3762/bjoc.9.276) - β3R3-Peptides: design and synthesis of novel peptidomimetics and their self-assembling properties at the air–water interface, Org. Biomol. Chem. 2013, 11(33), 5399-5403
Mosca, C. Dannehl, U. Möginger, G. Brezesinski, , L. Hartmann
(See online at https://doi.org/10.1039/c3ob41135d) - Amphiphilic Cationic β3R3-Peptides: Membrane Active Peptidomimetics and Their Potential as Antimicrobial Agents Biomacromolecules, 2014, 15 (5), 1687–1695
S. Mosca, J. Keller, N. Azzouz, S. Wagner, A. Titz, P. H. Seeberger, G. Brezesinski, and L. Hartmann
(See online at https://doi.org/10.1021/bm500101w) - Carbohydrate-Lectin Recognition of Sequence-Defined Heteromultivalent Glycooligomers J. Am. Chem. Soc., 2014, 136, 2008−2016
D. Ponader, P. Maffre, J. Aretz, D. Pussak, N.M. Ninnemann, S. Schmidt, P. H. Seeberger, C. Rademacher, G. U. Nienhaus, L. Hartmann
(See online at https://doi.org/10.1021/ja411582t) - “Label-free method for the detection of analytes based on soft hydrogel particles“ International application Nr.: PCT / EP 2014 / 050163
Schmidt, S.; Hartman, L.; Pussak, D.; Pompe, T.
