Concordia University

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Guest speakers

Dr. Andrei K. Yudin

Professor, Department of Chemistry
University of Toronto
Development of bioactive molecules using the tools of chemical synthesis

Production of molecules with desired functional attributes is the enduring objective of chemical synthesis. As structural complexity of therapeutic agents increases, so is the number of interrelated parameters that need to be controlled. Bioactive macrocycles offer a good example underscoring this notion. Their relatively large polar surface area increases the chance to interrogate extended protein binding sites, but also creates an impediment to achieving favorable drug properties. Synthetic tools that allow one not only to cyclize linear precursors but also to exercise control over conformation-driven cellular permeability are in high demand. This part of the lecture will summarize our ongoing efforts in this area and will highlight key experimental findings obtained in the past few months.

Another active area of our research targets biologically active boron-containing molecules. Boron is an abundant element on earth yet, despite its availability, C-B bonds are not present in the structures of natural products. This, however, does not mean that boron has no utility in chemical biology and drug discovery. On the contrary, there are numerous examples of bioactive molecules that bear C-B bonds. Similar to the synthetic utility of organoboron compounds, the biological activity of boron-containing molecules is based on reversible covalent interactions with nucleophiles. I will present the foundational principles of Boroscan – an enabling technology to construct boron-containing bioactive molecules using amphoteric molecules.

Andrei K. Yudin
Bio

Andrei K. Yudin received his undergraduate degree at the Moscow State University in 1992. He subsequently worked in the laboratories of G. K. S. Prakash and George A. Olah at USC, where he received his PhD in 1996. Following postdoctoral training in the laboratory of K. Barry Sharpless at the Scripps Research Institute, Professor Yudin started his independent career at the University of Toronto in 1998. He became an associate professor in 2002, which was followed by promotion to the rank of a full professor in 2007. Since January 2015, Professor Yudin has served as the Chair of the Board for Organic and Biomolecular Chemistry (a publication of the Royal Society of Chemistry, U.K.). He is an internationally renowned scholar who has created new molecules that serve as powerful tools used for chemical synthesis. Professor Yudin’s concept of “forced orthogonality” has enabled the development of entirely new classes of compounds, previously thought to be too unstable to be used as practical reagents. Professor Yudin has also been active in translating these fundamental discoveries into applications that impact the fields of chemistry, biology and medicine. Professor Yudin has been recognized with a number of awards. He is a fellow of the Royal Society of Chemistry (UK), and is a Fellow of the Royal Society of Canada.


Dr. Ka Yee C. Lee

Professor, Department of Chemistry
University of Chicago
The chemistry of breathing:  Wrinkle-to-fold transitions in lung surfactants and other elastic sheet

Lung surfactant is a mixture of lipids and proteins that coats the alveoli, and its main mechanical function is to reduce the work of breathing by reducing the surface tension. Insufficient amount of lung surfactant in premature infants leads to neonatal respiratory distress syndrome, while lung trauma can result in acute respiratory distress syndrome. In order to develop effective treatment for these conditions, a better understanding of the interactions between lung surfactant lipids and proteins is needed.  Utilizing optical and atomic force microscopy techniques, we have examined the collapse process in lung surfactant, and have examined how the presence of lung surfactant peptide, SP-B1-25, induces a reversible collapse in lung surfactant monolayers. Our observation indicates that SP-B1-25 in simple phospholipid and model lung surfactant monolayers promote the protrusion of folds into the subphase at low surface tensions.  The folds remain attached to the monolayer and reversibly reincorporated upon expansion.  Without SP-B, an unsaturated lipid-rich phase is irreversibly "squeezed-out" of the monolayer at higher surface tensions.  These folded reservoirs reconcile how lung surfactant can achieve both low surface tensions upon compression and rapid respreading upon expansion, and have important implications concerning the design of replacement lung surfactants. The onset of this folding instability can be understood in terms of the mechanical properties of the film. Statistics of the folding events will be presented and the link between folding on monolayers of nm thickness and that on polyester films that are 3 orders of magnitude thicker will be discussed. By studying different types of monolayers, we have shown that this folding transition in monolayers is not limited to lung surfactant films, but rather represents a much more general type of stress relaxation mechanism. Our study indicates that collapse modes are found most closely linked to in-plane rigidity. We characterize the rigidity of the monolayer by analyzing in-plane morphology on numerous length scales. More rigid monolayers collapse out-of-plane via a hard elastic mode similar to an elastic membrane, with the folded state being the final collapse state, while softer monolayers relax in-plane by shearing. For the hard elastic mode of collapse, we have further demonstrated experimentally and theoretically that the folded state is preceded by a wrinkled state.

Ka Yee C. Lee (Abstract figure)

 

 

Ka Yee C. Lee
Bio

Ka Yee C. Lee, Professor of the University of Chicago Chemistry Department, the James Franck Institute, Institute for Biophysical Dynamics and the College, also serves as the Senior Associate Vice President for Research. She leads efforts in the Office of the Executive Vice President for Research, Innovation and National Laboratories to support research program development across campus, incorporating the combined research strengths of Argonne, Fermilab and the Marine Biological Laboratory.  She currently serves as the Chair of the Faculty Advisory Committee of the UChicago Center in Hong Kong. Her research interests are in the area of biophysics, and her laboratory is engaged in several projects, examining the differential recognition of phosphatidylserine by immnoreceptors, the membrane sealing capabilities of poloxamers, the targeting selectivity of antimicrobial peptides, the role of cholesterol in lipid ordering in membrane (lipid rafts), the interactions of lung surfactant peptides and lipids, and biomimetic materials. She was a Searle Scholar, a Packard Fellow and a Sloan Research Fellow. Ka Yee obtained her Sc.B. in Electrical Engineering from Brown University, her M.S. and Ph.D. in Applied Physics from Harvard University. 


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