Our speaker for the September meeting of the Eastern NY Section of the ACS will be Dr. Robert Linhardt, the Ann and John H. Broadbent, Jr. ’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering, Chemistry and Chemical Biology at Rensselaer Polytechnic Institute. He will be presenting his recent work on the characterization of glycosaminoglycan and coronavirus (SARS-CoV-2) spike glycoprotein binding interactions.
This month’s section meeting will be held on September 16th starting at 6 PM. The meeting will be held online via WebEx. See below for details regarding how to join the meeting.
6:00-7:00 Happy Hour
7:00-7:30 Business Meeting
7:30-8:30 Research Presentation
The September meeting will be held virtually in Webex via this link.
Webex will download some software and then you will be able to connect to the meeting.
ABOUT THE PRESENTATION
Title: Characterization of glycosaminoglycan and coronavirus (SARS-CoV-2) spike glycoprotein binding interactions.
Abstract: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs may interact SARS-CoV-2 SGPs to facilitate host cell entry. We found that both monomeric and trimeric SARS-CoV-2 spike bind more tightly to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 μM, 0.12 μM, and 26.4 μM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. The current study serves a foundation to further investigate biological roles of GAGs in SARS-CoV-2 pathogenesis. Furthermore, our findings may provide additional basis for further heparin-based interventions for COVID-19 patients exhibiting thrombotic complications.
ABOUT OUR SPEAKER
Robert J. Linhardt
Robert J. Linhardt received his Ph.D. degree from the Johns Hopkins University (1979) and was a postdoctoral student with Professor Robert Langer at the Massachusetts Institute of Technology (1979-1982) and served on the faculty of University of Iowa from 1982-2003. He is currently the Ann and John H. Broadbent, Jr.’59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering at Rensselaer Polytechnic Institute, holding joint appointments in the Departments of Chemistry and Chemical Biology, Biology, Chemical and Biological Engineering, and Biomedical Engineering. He is an Adjunct Professor of Orthopedics at the Icahn School of Medicine, Mount Sinai, NY. His honors include the American Chemical Society Horace S. Isbell, Claude S. Hudson and Melville L. Wolfrom Awards, the AACP Volwiler Research Achievement Award, the USP Award for an Innovative Response to a Public Health Challenge, is a fellow of the National Academy of Inventors (NAI), a Fellow of the AAAS, and one of the Scientific American Top 10. His research focuses on glycobiology, glycochemistry and glycoengineering. He has recently been actively involved in the emerging field of nanobiotechnology and is focused on developing an artificial Golgi and cellulose-based energy storage devices. Professor Linhardt has published over 900 peer-reviewed manuscripts and holds over 50 patents.
Marquette University, B.S. 1975 Chemistry The Johns Hopkins University M.A., Ph.D. 1977, 1979 Organic Chemistry Massachusetts Institute of Technology Postdoctoral 1979-1982 Biochemical Engineering
Analytical and Bioanalytical Chemistry
Biochemistry and Chemical Biology
Biotechnology and Biomaterials
Organic, Medicinal and Drug Discovery
Polymers, Materials and Energy
Tip-enhanced Raman imaging of single-stranded DNA with single base resolution, Z. He, Z. Han, M. Kizer, R. Linhardt, X. Wang, A. Sinyukov, J. Wang, V. Deckert, A. Sokolov, J. Hu, M. Scully, Journal of the American Chemical Society, in press, 2018.
A mutant cell library for systematic analysis of heparan sulfate, H. Qiu, S. Shi, J. Yue, M. Xin, A. V. Nairn, L. Lin, X. Liu, G. Li, S. A. Archer-Hartmann, M. Dela Rosa, M. Galizzi, S. Wang, F. Zhang, P. Azadi, T. H. van Kuppevelt, W. V. Cardoso, K. Kimata, X. Ai, K. W. Moremen, J. Esko, R. J. Linhardt, L. Wang, Nature Methods, 15, 889-899, 2018.
A Flexible Carbon/Sulfur-Cellulose Core-Shell Structure for Advanced Lithium–Sulfur Batteries, L. Li, L. Hou, J. Cheng, T. J. Simmons, F. Zhang, L. Zhang, R. J. Linhardt, N. Koratkar, Energy Storage Materials, 15, 388–395, 2018.
Structural and functional components of the skate sensory organ ampullae of Lorenzini, X. Zhang, K. Xia, L. Lin, F. Zhang, Y. Yu, K. St.Ange, X. Han, E. Edsinger, J. J. Sohn, R. J. Linhardt, ACS Chemical Biology, 13, 1677–1685, 2018.
Sequencing the dermatan sulfate chain of decorin, Yanlei Yu, Jiana Duan, Franklin E Leach III, Toshihiko Toida, Kyohei Higashi, Hong Zhang, Fuming Zhang, I Jonathan Amster, Robert J Linhardt, Journal of the American Chemical Society, 139, 16986–16995, 2017.
Synthetic oligosaccharides can replace animal-sourced low-molecular weight heparins, Y. Xu, K. Chandarajoti, X. Zhang, V. Pagadala, W. Dou, D. M. Hoppensteadt, E. Sparkenbaugh, B. Cooley, S. Daily, N. S. Key, D. Severynse-Stevens, J. Fareed, R. J. Linhardt, R. Pawlinski, J. Liu, Science Translational Medicine, 9, eaan5954, 2017.
Nanostructured glycan architecture is important in the inhibition of influenza A virus infection, S.-J. Kwon, D. H. Na, J. H. Kwak, M. Douaisi, F. Zhang, E. J. Park, J.-H. Park, H. Youn, C.-S. Song, R. S. Kane, J. S. Dordick, K. B. Lee, R. J. Linhardt, Nature Nanotechnology, 12, 48-56, 2017.
The US regulatory and pharmacopeia response to the global heparin contamination crisis, A. Y. Szajek, E. Chess, K. Johansen, G. Gratzl, E. Gray, D. Keire, R. J. Linhardt, J. Liu, T. Morris, B. Mulloy, M. Nasr, Z. Shriver, P. Torralba, C. Viskov, R. Williams, J. Woodcock, W. Workman, A. Al-Hakim, Nature Biotechnology, 34, 625–630, 2016.