1. Department of Chemistry Seminar Announcement Date/Time/VenueTitle/Speaker 21 Jan (Fri) 3pm – 4pm @ S8 Level 3 Executive Classroom Following polypeptide folding and assembly with conformational switches Professor Beate Koksch Free University Berlin, Germany Host : Assoc Prof Suresh Valiyaveettil About the Speaker All are Welcome Professor Beate Koksch received her Diploma in Chemistry from University Leipzig. There, she earned her Ph.D. in biochemistry under supervision of Professor H.-D. Jakubke in 1995. She was a DFG research fellow in the laboratories of Professeor M. R. Ghadiri and Professor C.F. Barbas III at The Scripps Research Institute, La Jolla. In 2000 she returned to the University Leipzig to start her independent career. In June 2004 she assumed a position as Professor for Organic Chemistry and Natural Product Chemistry at the Free University Berlin. Her research interests focus on the interface of Abstract chemistry and biology and in particular on the role of complementary interactions and cooperativity on peptide and protein folding. Conformational transitions are a crucial factor in the vast majority of protein misfolding diseases. In most of these cases, the change in conformation is accompanied by the formation of insoluble aggregates, which often precludes a detailed characterization at the molecular level. Transitions are extraordinarily complex processes that are to date not fully understood on a molecular level. Therefore, much effort has been put into the development of simplified, easy-to-synthesize peptide models that can be used to elucidate the molecular processes that underlie the conformational switch. This talk is focussed on comparatively small, switchable peptide models developed by the Koksch laboratory. These peptide models are accessible using the synthetic methodology of bioorganic and peptide chemists and are organized according to the external stimulus that initiates and controls the structural transition. These model systems have already been shown to serve well in following the interconversion of certain secondary structures depending on factors such as pH, ionic strength, metal ions, chaperones or solvents. With these peptide models it is possible to study such important and complex issues as the role of electrostatic interactions as well as of metal ions in aggregation processes in the context of all other environmental conditions at the molecular level applying high resolution analytical methods. The strategies introduced additionally exhibit outstanding potential to be used for the development of novel, self-assembling bio-inspired materials or sensors.

2. Department of Chemistry Seminar Announcement Date/Time/VenueTitle/Speaker 24 Jan (Mon) 3pm – 4pm @ S8 Level 3 Executive Classroom Fluorine Meets Peptides Professor Beate Koksch Free University Berlin, Germany Host : Asst Prof Zeng Huaqiang About the Speaker All are Welcome Professor Beate Koksch received her Diploma in Chemistry from University Leipzig. There, she earned her Ph.D. in biochemistry under supervision of Professor H.-D. Jakubke in 1995. She was a DFG research fellow in the laboratories of Professeor M. R. Ghadiri and Professor C.F. Barbas III at The Scripps Research Institute, La Jolla. In 2000 she returned to the University Leipzig to start her independent career. In June 2004 she assumed a position as Professor for Organic Chemistry and Natural Product Chemistry at the Free University Berlin. Her research interests focus on the interface of Abstract chemistry and biology and in particular on the role of complementary interactions and cooperativity on peptide and protein folding. Despite its low abundance in naturally occurring biomolecules, fluorine’s favorable impact on the pharmacokinetics and biological properties makes it an outstanding element for peptide and protein modification. Fluorine’s effects trace back to its unique physicochemical properties, which are a very high electronegativity and electron affinity combined with a very low polarizability and high stability of the carbon-fluorine bond. As fluoroalkyl groups uniquely combine two contrary properties - polarity and hydrophobicity - their effects as substituents in native proteins are not easily predicted. We have developed peptide-based models to systematically studying the complex molecular interactions of fluoroalkyl groups within native polypeptides regarding space filling, lipophilicity and hydrogen-bonding. Using these in vitro investigations we determined how fluorinated amino acids influence the folding of native polypeptide motifs and established the key influence of the fluorine-fluorine interactions on peptide and protein folding. The combination of the peptide model with analytical techniques and screening methods such as surface plasmon resonance (SPR) and phage display technology creates perfect systems that allow to studying the interaction pattern of a variety of fluorinated residues with all kinds of hydrophobic as well as charged amino acid side chains, respectively, within polypeptide environments. These studies pave the way for using the beneficial properties of fluorinated amino acids for the deliberate de novo design of biologically relevant peptide drugs as well as of fluorinated protein- based materials.

3. Department of Chemistry Seminar Announcement Date/Time/VenueTitle/Speaker 28 Jan (Fri) 3pm – 4pm @ S8 Level 3 Executive Classroom  /  /  Peptide chimeras to generate artificial helical folding motifs Professor Beate Koksch Free University Berlin, Germany Host : Asst Prof Chan Yin Thai About the Speaker All are Welcome Professor Beate Koksch received her Diploma in Chemistry from University Leipzig. There, she earned her Ph.D. in biochemistry under supervision of Professor H.-D. Jakubke in 1995. She was a DFG research fellow in the laboratories of Professeor M. R. Ghadiri and Professor C.F. Barbas III at The Scripps Research Institute, La Jolla. In 2000 she returned to the University Leipzig to start her independent career. In June 2004 she assumed a position as Professor for Organic Chemistry and Natural Product Chemistry at the Free University Berlin. Her research interests focus on the interface of Abstract chemistry and biology and in particular on the role of complementary interactions and cooperativity on peptide and protein folding. The attempt to construct nature’s architecture from non-natural building blocks has challenged scientists for many decades. One goal of this field of study is to overcome the intrinsic protease- susceptibility of natural peptides which limits their clinical use. Peptides composed of homologous amino acids, those that have additional backbone methylene units compared to the natural  -amino acids, are at present among the most widely studied bio-mimetic oligomers that adopt well-defined conformations (foldamers). The wide variety of specific secondary structures that can be adopted by  - and  -peptides becomes especially valuable for the design of higher levels of organization such as tertiary or quaternary structures. Previous efforts towards this goal employing  -amino acid building blocks lead to the discovery of both homomeric and heteromeric helix bundles and helical inhibitors of protein-protein interactions; however, there are significant differences between the packing observed in these artificial quaternary assemblies and that of the corresponding natural assemblies. This phenomenon has thus far impeded the combination of both classes into compact protein-like chimeric structures. The focus of our research in this area is to identify extended sequences of  - and  -amino acids that can be incorporated into  -helical coiled coil-based sequences to produce artificial chimeric folding motifs. Such artificial motifs with their orthogonal structural elements are great candidates to be incorporated into natural helical proteins. Because protein-protein interactions involving helical domains determine specificity for important biological processes such as transcriptional control, cellular differentiation, and replication, selective disruption should be an excellent strategy for drug discovery. Our results represent the first examples of the “isosteric” substitution of entire heptad repeats in  - helical coiled coil motifs by non-natural fragments consisting of extended sequences of alternating  - and  -amino acids with retention of global conformation and the stability of the fold. Our results facilitate a new direction in protein engineering toward modular replacement of extended helical segments with non-proteinogenic fragments in biological important helical protein domains with possible applications in biology, pharmacy, and medicine.