Project Area A A1: Protein-recognition by supramolecular ligands from focused combinatorial libraries

Project A1 generates and examines relatively small focussed combinatorial libraries of linear, multiarmed and branched peptidic dendrimers in two alternative approaches. With the “split-and-mix” method screening and determination of protein affinities as well as inhibitory properties will be performed “on-bead” using solid-phase bound libraries. Hit candidates will be synthesized in larger amounts for subsequent mechanistic studies as well as structural elucidation. In dynamic combinatorial libraries two or more building blocks are covalently connected by reversible transformations such as imine or hydrazone formation. Suitable screening and deconvolution strategies will allow to identify potent protein ligands.

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Curriculum Vitae of Prof. Dr. Carsten Schmuck †

Professional career

2008-2019	Full Professor (W3) of Organic Chemistry, University of Duisburg-Essen
2002-2008	Professor (C3) of Organic Chemistry, University of Würzburg
1997-2001	Assistant professor at the University of Cologne, Department of Organic Chemistry
1995-1997	Postdoctoral Research Assistant with Prof. Dr. R. Breslow, Department of Chemistry, Columbia University, New York

Scientific education and degrees

2001	Habilitation and Venia legendi (Organic Chemistry) at the University of Cologne, Mentor: Prof. Dr. A. Berkessel
1992-1994	Ph.D. at the Ruhr-University Bochum with Prof. Dr. W. R. Roth
1987-1992	Study of Chemistry (Dipl.) at the Ruhr-University Bochum, Diploma thesis with Prof. Dr. W. R. Roth, Bochum

 

Selected Publications

M. Li, M. Radic Stojkovoic, M. Ehlers, E. Zellermann, I. Piantanida, C. Schmuck: Use of an octapeptide - guanidiniocarbonylpyrrol conjugate for the formation of a supramolecular beta-helix which further self-assembles into pH responsive fibers. Angew. Chem. Int. Ed. 2016, 55, 1301.

M. Li, M. Ehlers, S. Schlesiger, E. Zellermann, S. Knauer, C. Schmuck: Incorporation of a Non-Natural Arginine Analogue into a Cyclic Peptide Leads to Formation of Positively Charged Nanofibers Capable of Gene Transfection. Angew. Chem. Int. Ed. 2016, 55, 598.

Q.-Q. Jiang, W. Sicking, M. Ehlers, C. Schmuck: Discovery of potent inhibitors of human β-tryptase from pre-equilibrated dynamic combinatorial libraries. Chem. Sci. 2015, 6, 1792.

H. Y. Kuchelmeister, S. Karczewski, A. Gutschmidt, S. Knauer, C. Schmuck: Utilizing Combinatorial Chemistry and Rational Design: Peptidic Tweezers with Nanomolar Affinity to DNA can be transformed into Efficient Vectors for Gene Delivery by Addition of a Lipophilic Tail. Angew. Chem. 2013, 125, 14266.

H. Y. Kuchelmeister, A. Gutschmidt, S. Knauer, C. Schmuck: Efficient Gene Delivery into Cells by a Surprisingly Small Three-Armed Peptide Ligand. Chem. Sci. 2012, 3, 996.

J. Wu, Y. Zou, W. Sicking, I. Piantanida, T. Yi, C. Schmuck: A Molecular Peptide Beacon for the Ratiometric Sensing of Nucleic Acids. J. Am. Chem. Soc. 2012, 134, 1958.

S. Niebling, H. Y. Kuchelmeister, C. Schmuck, S. Schlücker: Quantitative label-free monitoring of peptide recognition by artificial receptors: A comparative FT-IR and UV resonance Raman spectroscopic study. Chem. Sci. 2012, 3, 3371.

 J. Wu, A. Zawistowski, M. Ehrmann, T. Yi, C. Schmuck: Peptide functionalized Polydiacetylene Liposomes act as a Fluorescent Turn-On Sensor for Bacterial Lipopolysaccharide. J. Am. Chem. Soc. 2011, 133, 9720–9723

P. R. Wich, C. Schmuck: Reversible and Non-Competitive Inhibition of β-Tryptase by Protein Surface Binding of Tetravalent Peptide Ligands Identified from a Combinatorial Split-Mix-Library. Angew. Chem. Int. Ed. 2010, 49, 4113 –4116.

N. J. V. Lindgren, L. Geiger, J. Razkin, C. Schmuck, Lars Baltzer: Downsizing Enzymatic Function by Chemical Methods – Arginine Mimics with Low pKa Values Increase Rates of Hydrolysis of RNA Model Compounds. Angew. Chem. Int. Ed. 2009, 48, 6722.