Welcome to the second episode of Season 3 of JAWSChem! Our next webinar will take place via the internet on Tuesday April 27th at 8PM EDT/1AM GMT (April 28th). Sign up on our mailing list to receive the Zoom link!
We hope to see/hear from you all at one of our sessions or as one of the next speakers. If you are an early career scientist and would like to present your research, don't hesitate to submit an abstract today! For now, please learn more about our current speakers and their research below!
Our featured speakers this week are Dr. Zeus de los Santos (postdoctoral researcher, National Institute of Standards and Technology, USA) and Prof. Stacy Malaker (assistant professor, Yale University, USA). The seminar will be guest moderated by Prof. Beth Elacqua from Penn State University!
LEARN MORE ABOUT THE SPEAKERS AND THEIR TALKS BELOW
DR. ZEUS DE LOS SANTOS
Biography: Zeus De los Santos is an NRC Postdoctoral Research Associate at the National Institute of Standards and Technology (NIST) in Gaithersburg, MD. He obtained his Ph.D. from Georgetown University in the lab of Prof. Christian Wolf, where he worked on designing multiple analytical assays geared towards high-throughput sensing of chiral compounds. At NIST, he is currently applying his expertise on chirality and molecular recognition to study the binding phenomena and subsequent spectroscopic changes between exogenous substrates and (a)chiral single-wall carbon nanotubes to develop a substrate-agnostic sensing platform akin to a molecular perceptron.
Title of Talk: Development of Analytical Assays for Direct Sensing of Chiral Molecules
Abstract: With the advent of high-throughput experimentation, hundreds of asymmetric reactions can now be conducted in parallel. Traditional methods used to analyze chiral compounds from asymmetric reaction mixtures are intrinsically serial, time-consuming and generate copious amounts of chemical waste. In recent years, chiroptical sensing with CD spectroscopy has become a popular alternative to address the growing need for automated high-speed chirality analysis. In this talk, I will focus on two of the assays we have designed in the Wolf group. First, a stereodynamic ligand capable of Schiff-base formation and concomitant coordination to a Pd(II) center was developed for sensing amine-containing compounds. This assay was applied in the concentration, enantiomeric excess (ee), and absolute configuration determination of a chiral amine produced by an asymmetric hydrogenation of an iminium salt. This analysis required only 1.0 mg of the crude reaction mixture and minimized cost, labor, time and waste when compared to traditional analytical techniques frequently used to obtain stereochemical information. Next, I will discuss an optical method we have created for the accurate concentration, and simultaneous enantiomeric (er) and diastereomeric ratio (dr) determination of amino alcohols based on a simple and practical mix-and-measure protocol. The reaction with salicylaldehyde and a Cu(II) salt was found to produce spectroscopic signals that allow quantitative analysis of each stereoisomer of 1-amino-2-indanol through a combination of UV-Vis and CD spectroscopy signal deconvolutions. Applying machine learning using linear programming methodology to optimize weighting of spectroscopic signals and a parameter sweep algorithm for unbiased identification of optimal wavelength ranges, the concentration and complete speciation of each of the four stereoisomers in 20 samples of vastly different stereoisomeric compositions were determined with very low averaged absolute errors.
PROF. STACY MALAKER (on twitter @StacyMalaker)
Biography: Dr. Malaker is an Assistant Professor in the Department of Chemistry at Yale University. Her laboratory is focused on establishing methods and technology to study mucins, a class of densely O-glycosylated extracellular proteins, by MS. Additionally, the laboratory studies mucins in a biological context, since these proteins play integral, yet poorly understood, roles in numerous diseases. Prior to her appointment at Yale, she received her B.S. from the University of Michigan in Biochemistry and Anthropology-Zoology. Dr. Malaker then went on to receive her PhD in Chemistry from the University of Virginia in the laboratory of Professor Donald Hunt. She continued to investigate the role of aberrant glycosylation in cancer as an NIH postdoctoral fellow in Professor Carolyn Bertozzi’s laboratory at Stanford University before starting at Yale in 2021.
Title of Talk: Revealing the Human Mucinome
Abstract: Mucin domains are densely O-glycosylated modular protein domains found in a wide variety of cell surface and secreted proteins. Mucin-domain glycoproteins are key players in a host of human diseases, especially cancer, but the scope of the mucinome remains poorly defined. Recently, we characterized a bacterial mucinase, StcE, and used its unique properties to improve analysis of mucin-domain glycoproteins by mass spectrometry. Further, we demonstrated that an inactive point mutant retains binding selectivity for mucins. In this work, we leveraged inactive StcE to selectively enrich and identify mucins from complex samples like cell lysate and crude ovarian cancer patient ascites fluid. Our enrichment strategy was further aided by an algorithm to assign confidence to mucin-domain glycoprotein identifications. This mucinomics platform facilitated detection of hundreds of glycopeptides from mucin domains and highly overlapping populations of mucin-domain glycoproteins from ovarian cancer patients. Ultimately, we demonstrate our mucinomics approach can reveal key molecular signatures of cancer from in vitro and ex vivo sources.
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