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Organic Chemistry Seminar

Friday, April 19, 2019
4:00pm to 5:00pm
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Noyes 147 (J. Holmes Sturdivant Lecture Hall)
Molecular Recognition in Chemical and Biological Systems: Chemical Models and Biostructural Investigations
François Diederich, Professor of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich,

We pursue in a multi-dimensional approach the quantification of weak intermolecular interactions in chemical and biological systems. Examples discussed in the lecture are orthogonal dipolar interactions, organofluorine interactions, substituent effects on π-π-stacking interactions, halogen bonding, and chalcogen bonding. Enantioselective complexation based solely on dispersion interactions and perfect shape complementarity is achieved with new chiral alleno-acetylenic cage compounds. We also explore the energetics of the replacement of conserved water molecules in protein co-crystal structures by ligand parts, with a particular interest in cyclic water clusters. Lessons learned are directly applicable to ligand design and optimization in drug discovery and crop protection research, but equally to the assembly of synthetic supramolecular systems.

The approach is illustrated in examples taken from our structure-based drug design projects. Specific examples for investigations of protein-ligand interactions include (i) addressing the Gly-rich ATP-triphosphate-binding loop of protein kinase A (PKA), (ii) complexation at the allosteric site of IspD, an enzyme from the non-mevalonate pathway of isoprenoid biosynthesis and deciphering of the allosteric mechanism, (iii) halogen-bonding at the active site of the cysteine protease hCatL, and (iv) ligand development against a novel target for antimalarials, serine hydroxymethyl transferase (SHMT), a key enzyme from the folate biosynthesis cycle.

For more information, please contact Vicky Brennan by phone at 626-395-6151 or by email at [email protected].