Research

Two approaches are typically used for the synthesis of protein-polymer conjugates, grafting-to and grafting-from. During grafting-to, the polymer is synthesized first and subsequently conjugated to the protein. For grafting-from, a polymerization initiator or mediator is linked to the protein followed by grafting the polymers directly from the protein surface. The third, seldom used technique, grafting-through, consists of the polymerization of peptide or protein monomers to incorporate several biomolecules in the polymer backbone. Grafting-to and grafting-from suffer from low specificity, especially when targeting the abundant lysine residues. Enzymatic strategies are a promising approach for a site-specific polymer attachment. We are currently using sortase-mediated ligation (SML) for C- or N-terminal modification of proteins.

RSC Adv., 2019, 9, 4700

Polym. Chem., 2015, 6, 5143

Enzymes are very attractive alternatives to conventional catalysts due to their high specificity, versatility and adaptability. They became increasingly popular in the last two decades to establish sustainable syntheses. However, stability and reusability are challenging for most enzymes. We are addressing this issue by covalent conjugation of polymers and immobilization of the biocatalysts on polymeric support materials. The aim is to enable use at higher temperatures and over longer periods of time. Site-specific conjugation strategies can be helpful here in order to maintain a high activity of the enzyme. In addition, polymers that can be specifically tailored to the surface properties of enzymes can form non-covalent enzyme/polymer complexes. We were able to show that the enzyme activity in such complexes can be significantly increased compared to the unmodified enzyme.

Cooperation partners:

Prof. Dr. Leilei Zhu, Tianjin Institute of Industrial Biotechnology TIB, China

Dr. Antje Lieske, Fraunhofer Institute for Applied Polymer Research IAP, Potsdam

Dr. Mehdi D. Davari, Leibniz Institute for Plant Biochemistry IPB, Halle

Prof. Dr. Katja Arndt, University of Potsdam

Dr. Martin Reifarth, University of Potsdam

ChemCatChem, 2024, 16, e202301685

Angew. Chem. Int. Ed., 2018, 57, 13810

The high specificity of proteins may be advantageous for therapeutic applications compared to small molecule drugs. However, therapeutic proteins are often recognized by the immune system and quickly cleared from the body. It was found in the 1970s that the conjugation of poly(ethylene glycol) (PEG), now known as PEGylation, can shield a protein. As a result, the immunogenicity is reduced and the protein less prone to thermal denaturation, aggregation and degradation by proteases. However, many of the around 20 clinically approved protein-PEG conjugates come along with reduced efficacy, mainly caused by polymer conjugation to random sites in the protein. Furthermore, the development of anti-PEG antibodies, leading to quick clearance of PEGylated drugs, demonstrates that other polymers should be considered for future therapeutic conjugates. We take advantage of our portfolio of protein-polymer conjugation strategies to better understand how to optimize the stabilization of therapeutic proteins. On the one side, we compare different conjugation approaches in their effect on protein structures and functions. On the other side, we synthesize various polymers that are considered as alternatives to PEG and apply them in therapeutic conjugates.

Cooperation partner:

Prof. Dr. Heiko Möller, University of Potsdam

Macromol. Chem. Phys., 2023, 224, 2200353

J. Drug Deliv. Sci. Technol., 2023, 79, 103995

With the emergence of COVID-19, viral infections came into the focus of society, applied and basic research. To date, there are hardly any drugs against viral diseases. SARS-CoV-2 enters human cells after binding of its trimeric spike protein to ACE 2 receptors. Antibodies that bind to surface proteins of viruses and block their interaction with ACE 2 receptors are a therapeutic approach. As the production of antibodies is complex and expensive, nanobodies, small fragments of antibodies, are seen as a potent alternative in basic research. The nanobody Ty1, obtained from alpacas, showed a high potential to neutralize SARS-CoV-2. We synthesize Ty1-polymer conjugates and investigate their stability and potential for virus neutralization. This showed a clear influence of the polymer used, which could open up a wide range of therapeutic options against viral diseases in the future.

Cooperation partner:

Prof. Dr. Petra Wendler, University of Potsdam

Lanthanides are of enormous economic importance for many areas of the high-tech industry. They are currently difficult to extract and separate using environmentally hazardous chemicals. As a new approach from the bioeconomy, we are using highly selective peptides with the long-term goal of contributing to sustainability and circular economy. We are currently investigating the extent to which peptide/lanthanide complexation is influenced by polymer conjugation and immobilization.

Cooperation partners:

Prof. Dr. Michael Kumke, University of Potsdam

Prof. Dr. Heiko Möller, University of Potsdam

Dr. Björn Drobot, Helmholtz Center Dresden-Rossendorf

Dr. Franziska Lederer, Helmholtz Center Dresden-Rossendorf

RSC Adv., 2024, 14, 14091

DFG: "Biohybrid Materials", Heisenberg grant, 02/2024 - 01/2027, project number 530253155

BMBF: “Enzyme Stabilization for a Circular (Bio-)Plastic Economy” (EnzCircEco), 01/2024 - 12/2026, FKZ 031B1424

BMBF: “The development and implementation of a COVId-19 scFv-TRAP portfolio for diagnostic and therapeutic applications” (COVITRAP), 11/2021 – 10/2023, FKZ 01DP21012

BMBF: “Let biology do the trick - Peptides enwind crucial raw materials: the “natural separation” of Lanthanides” (PepTight), 09/2021 – 05/2025, FKZ 031B1122B

Fraunhofer Leistungszentrum "Funktionsintegration": “Sortase-based protein-polymer and protein-nanoparticle conjugates: characterization of 3D-structure, dynamics and Interaction via NMR spectroscopy”, since 01/2020

DFG: “Enabling multiple linkages through sortase-mediated ligation”, 01/2019 – 03/2022, project number 414977640

BMBF: “Chiral Membranes II”, 02/2018 – 01/2021, FKZ 031B0559B