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Hi colleagues,
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<div class=""><span class="Apple-tab-span" style="white-space: pre;"></span>Sorry for multiple postings of this. For this Friday (Nov 16, 2018) QSB seminar I am happy to bring my colleague from the FDA who is both doing good research and also might be able
to provide insights into the drug approval process for those of you who are entrepreneurially minded. </div>
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<div class="">The speaker is Daron Freedberg, and the title of his talk (Abstract below) is "NMR of Glycans ON and OFF cells”. He is looking into why some saccharides do not induce an immune response, while others do, by looking at their structures.</div>
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<div class="">Please let me ( <a href="mailto:pliwang@ucmerced.edu" class="">pliwang@ucmerced.edu</a> ) know if you would like to speak or go to lunch with Daron next week, Friday Nov 16, 2018. <b class="">His talk will be 1:30-2:45pm, in GRAN 135.</b></div>
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<div class="">Cheers,</div>
<div class="">Patti</div>
<div class=""><a href="mailto:pliwang@ucmerced.edu" class="">pliwang@ucmerced.edu</a></div>
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<p class="MsoNormal" align="center" style="margin-bottom: 1pt; text-align: center; text-indent: 0.25in;">
<b class="">NMR of Glycans ON and OFF cells</b><o:p class=""></o:p></p>
<p class="MsoNormal" style="margin-bottom: 1pt; text-indent: 0.25in;">Carbohydrates are ubiquitous in nature and participate in a wide variety of cellular processes. They make up bacterial capsules, play roles in cell-cell interactions such as immune responses,
fertilization, inflammation, and cell growth, influence protein folding and stability, and may be involved in signal transduction. Given the variety of monosaccharides, linkage types, and functional group modifications, oligosaccharides alone have potential
structural complexity unmatched by any other biomolecule. <o:p class=""></o:p></p>
<p class="MsoNormal" style="text-indent: 0.25in;">Despite their importance, carbohydrate structure-function relationships, or “glycan code”, are poorly understood. Our group is delineating carbohydrate three-dimensional solution structure to gain insight into
how carbohydrates function, which should facilitate development of vaccines, drug delivery systems, and antibiotics of the future. Our goal is to unveil carbohydrate structure-function relationships using heteronuclear multidimensional NMR to delineate conformation
and dynamics of <sup class="">15</sup>N, <sup class="">13</sup>C enriched oligo- and polysaccharides.<o:p class=""></o:p></p>
<span class="" style="font-size: 12pt; font-family: Cambria, serif;">In recent research, we sought to understand why </span><span class="" style="font-size: 12pt; font-family: Symbol;">a</span><span class="" style="font-size: 12pt; font-family: Cambria, serif;">,
2->8 polysialic acid induces almost no immune response in humans, while other polysaccharides induce a stronger immune response. We hypothesized that a three-dimensional structural difference between polysaccharides on and off cells may be the source of this
difference. To test this hypothesis, we deciphered the structure of <sup class="">15</sup>N, and <sup class="">13</sup>C polysialic acid on bacteria and found that the structure is quite similar to purified polysialic acid. In a continuing effort to address
this question, we are studying </span><span class="" style="font-size: 12pt; font-family: Symbol;">a</span><span class="" style="font-size: 12pt; font-family: Cambria, serif;">, 2->8 tetrasialic acid in solution. Our recent studies of the labeled tetramer
show evidence for a helix with two residues per turn. Finally, we recently developed methods to observe hydrogen bonding involving hydroxyl groups in carbohydrates. We are able to directly detect hydrogen bonds and assign directionality. We also recently developed
methods to measure hydroxyl group H/D exchange rates in glycans, to infer hydrogen bonds in systems in which we cannot directly detect them . Direct detection of hydrogen bonds is a powerful structural descriptor since only certain conformations can explain
their presence. Therefore, hydrogen bonds, in opposition to other NMR observables, provide evidence of unique three-dimensional structures even when coexisting with other conformations in solution. Together, these experiments are helping to expand the repertoire
of methods available to determine carbohydrate three-dimensional solution structures.</span></div>
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