Chemical Ligands and Methods A3: Designed copolymers and molecular tweezers for protein surface recognition

In A3 inspection of protein crystal structures and theoretical simulations result in the selection of distinct methacrylamide-based monomers from a modular set of specific binders for all classes of amino acids. These mixtures will be subjected to radical copolymerization and later also to molecular imprinting, to produce specific protein surface binders as inhibitors of isolated digestive enzymes and HtrA proteases. In an alternative approach, powerful molecular lysine and arginine tweezers will be equipped with additional peptidic binding sites for their immediate protein environ-ment. These tailored molecular twezers will be directed to hot spots on proteins of all CRC partners.

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Curriculum Vitae

Professional career

Since 2006	Full Professor, Duisburg-Essen University
2000	Associate Professor, Marburg University
1991	Assistant Professor, Düsseldorf University
1989	Postdoc, Princeton University, USA (E. C. Taylor)

Scientific education and degrees

1998	Habilitation, Düsseldorf University (G. Wulff)
1988	Ph.D. (Organic Chemistry), Bonn University (W. Steglich)
1976-1985	Study of Chemistry (Diploma), Bonn University

Selected Publications

T. Schrader, G. Bitan, F.-G. Klärner: Molecular tweezers for lysine and arginine – powerful inhibitors of pathologic protein aggregation. Chem. Commun. 2016, 52, 11318-11334.

C. Streich, L. Akkari, C. Decker, J. Bormann, C. Rehbock, A. Müller-Schiffmann, F. C. Niemeyer, L. Nagel-Steger, D. Willbold, B. Sacca, C. Korth, T. Schrader, S. Barcikowski: Characterizing the Effect of Multivalent Conjugates of Aβ-specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation. ACS Nano. 2016, 10, 7582-7597.

E. Lump, L. M. Castellano, C. Meier, J. Seeliger, N. Erwin, C. M. Stürzel, S. Usmani, R. M. Hammond, J. von Einem, G. Gerold, F. Kreppel, K. Bravo-Rodriguez, T. Pietschmann, V. M. Holmes, D. Weissman, F. Kirchhoff, T. Weil, T. Schrader, G. Bitan, E. Sanchez-Garcia, R. Winter, J. Shorter, J. Münch: A molecular tweezer antagonizes seminal amyloid and HIV infection. eLife. 2015, 4, e05397.

D. H. J. Lopes, A. Attar, G. Nair, E. Y. Hayden, Z. Du, K. McDaniel, S. Dutt, H. Bandmann, K. Bravo-Rodriguez, S. Mittal, F.-G. Klärner, C. Wang, E. Sanchez-Garcia, T. Schrader, G. Bitan: Molecular tweezers inhibit islet amyloid polypeptide assembly and toxicity by a new mechanism. ACS Chem. Biol. 2015, 10, 1555-1569.

P. Latza, P. Gilles, T. Schaller, T. Schrader: Affinity Polymers Tailored for the Protein A Binding Site of Immunoglobulin G Proteins. Chem. Eur. J. 2014, 11479-11487.

F.-G. Klärner, T. Schrader: Aromatic Interactions by Molecular Tweezers and Clips in Chemical and Biological Systems. Special Issue “Aromatic Interactions in Chemistry and Biology”, Acc. Chem. Res. 2013, 46, 967–978.

R. Rose, K. Bravo-Rodriguez, J. M. Ramirez-Anguita, F.-G. Klärner, E. Sanchez-Garcia, T. Schrader, C. Ottmann: Molecular Tweezers modulate 14-3-3 Protein-Protein Interactions. Nat. Chem. 2013, 5, 234-239.

A. Attar, C. Ripoli, P. Maiti, S. Sinha, T. Liu, M. R. Jones, F. Yang, G. D. Gale, K. Lichti-Kaiser, C. Tseng, M. Tan, C. -W. Xi, J. L. Straudinger, F. -G. Klärner, T. Schrader, S. A. Frautschy, C. Grassi, G. Bitan: Protection of primary neurons and mouse brain from Alzheimer’s pathology by molecular tweezers. Brain. 2012, 135, 3735-3748.

K. Bernitzki, M. Maue, T. Schrader: Artificial Signal Transduction with a Primary and Secondary Messengers. Chem. Eur. J. 2012, 18, 13412-13417.

K. Hochdörffer, J. März-Berberich, L. Nagel-Steger, M. Epple, W. Meyer-Zaika, A. H.C. Horn, H. Sticht, S. Sinha, G. Bitan, T. Schrader: Rational Design of β-Sheet Ligands against Aβ42-induced toxicity. J. Am. Chem. Soc. 2011, 133, 4348-4358.