Proteomic Chemistry


The work of the Center for Proteomic Chemistry (CPC) lies at the intersection of the chemical and biological universes: CPC's mission is the systematic study of the interactions of small chemical molecules with biological macromolecules, generally proteins. One major focus of CPC is 'lead finding' - the identification of chemical compounds as starting points for medicinal chemistry that can then be optimized further into candidates for clinical development.

CPC collaborates closely with all of NIBR's departments, applying the suitable combination of lead finding approaches to each drug discovery project. These include high- and medium-throughput screening, structural biology, fragment-based drug discovery, biophysics, and various in silico approaches.

In partnership with Global Discovery Chemistry (GDC), CPC is the steward of the Novartis Compound Bank, a collection of over one million chemical compounds. We are actively engaged in expanding the chemical space represented in our library beyond low molecular weight compounds. For example, we are exploring the space around macrocyclic peptides and DNA encoded libraries. CPC also operates the IT and automation infrastructure for most compound logistics at NIBR.

Natural products, chemical compounds isolated from various natural sources such as microbes, fungi, and plants, are a special part of the compound collection. Their identification, isolation, and study are the focus of the CPC's Natural Products Unit (NPU). Furthermore, we are applying the methods of synthetic biology to natural product producing microorganisms in order to discover novel chemical matter.

Also part of CPC is the Expertise Platform Proteases (EPP), which was established to study an important target family, proteases. Many biological targets belong to distinct molecular families and tend to interact with small compounds in a very similar way, making it possible to apply lessons learned from one target to other similar targets and thus making drug discovery faster and more efficient.

CPC's scientific activities are made possible by substantial expertise in assay automation, compound logistics, information technology, cheminformatics, and the management and interpretation of vast amounts of experimental data.



Selected Publications

Large-scale prediction and testing of drug activity on side-effect targets. Lounkine E, Keiser MJ, Whitebread S, Mikhailov D, Hamon J, Jenkins JL, Lavan P, Weber E, Doak AK, Cote S, Shoichet BK, Urban L. Nature. 2012 Jun 10;486(7403):361-7

Natural products as catalysts for innovation: a pharmaceutical industry perspective. Schmitt E, Moore C, Krastel P, Petersen F. Curr Opin Chem Biol. 2011 Jun 18.

Protease-directed drug discovery. Sedrani R, Hommel U, Eder J. Gene Family Targeted Molecular Design. Edited by Lackey KE. 2009: 159-97.

Impact of high-throughput screening in biomedical research. Nature Reviews Drug Discovery 10, 188-195