Session II

Monday, May 22nd

Session II


1,4-Anhydroseptanoses: Serendipitous formation and their selective rupture toward synthesizing septanosyl glycosides

Aditya Pote, Raghu Vannam and Mark W. Peczuh

University of Connecticut, Department of Chemistry

Septanoses, seven membered ring carbohydrates, are synthetic analogs of pyranoses where an additional carbon atom has been added to the ring. Septanosides have shown activity as ligands of lectins as well as substrates for glycosidase enzymes. In the course of synthesizing carbohydrate based oxepines which are themselves useful starting materials for oligosaccharides, we discovered the formation of 1,4-anhydroseptanoses. The synthesis of the precursors of cyclization started with an addition of vinyl magnesium bromide onto pyranose lactols followed by ozonolysis. The hydroxy aldehyde products of this two-step sequence were trapped as their cyclic acetals via acetylation, giving 1,2-di-O-acetyl-3,4,5,6-tetra-O-benzyl septanoses. The 1,2-di-O-acetates were converted to their anomeric halides using HBr in acetic acid or iodotrimethylsilane followed by in situ intramolecular attack of a benzyl ether oxygen onto the anomeric carbon then gave rise to the new 1,4-anhydrosugars. Yields of the respective 1,4-anhydroseptanose analogs were moderate to high and the regioselectivity of the cyclization product was confirmed by 2D NMR techniques as well as X-ray crystallography. The transformation is relatively general and was extended to septanoses derived from mannose, xylose and galactose. A regioselective conversion of 1,4-anydro species to septanose glycosides in preference to furanoses was also demonstrated proving that these are valuable intermediates for oligomerization of septanose carbohydrates. We posit that the newly discovered 1,4-anhydroseptanoses can serve as effective starting materials for septanose-based conjugates. Optimization of the reaction conditions and scope of the nucleophiles for the selective opening 1,4-anhydrosugars to prove the utility of this method is to be studied in future.


Time series lipidomics analysis of green microalgae under nutrient stress

Eryn Matich, Mohsen Ghafari, Ersan Camgoz, Blaine A. Pfeifer, Berat Z. Haznedaroglu, and G. Ekin Atilla-Gokcumen

University at Buffalo, Department of Chemistry

The utilization of fossil fuels as energy sources leads to carbon dioxide and other gas emissions that contribute to global warming. As such, methods that can replace these with alternative, clean and renewable energy sources are of great interest. Many plants produce lipids such as triacylglycerols (TAGs) which are precursor molecules for biodiesel production. Microalgae present an attractive alternative since they have a higher oil yield than other plants and when grown under certain conditions they accumulate lipids and can be grown on water and therefore do not compete with agricultural land. The aim of this study is to analyze the changes in lipid-derived value added metabolites produced by microalgae under different growth conditions to gain information at the molecular level to understand the metabolic processes that accompany these changes. We chose a highly-adaptable, oleaginous, non-model microalgae, Ettlia oleaobundans. We developed a MS-based metabolomics method to analyze the changes in metabolites under different growth conditions using LC-Q-ToF, under nitrogen and phosphorous replete (N+, P+) and deplete (N-, P-) conditions. Untargeted and targeted analysis of the changes in metabolite composition highlighted the accumulation of TAGs and depletion of chlorophylls and certain structural lipids for photosynthesis under nutrient deprived conditions. In addition, we found a correlation between the changes in certain plant lipids under N- and P- conditions, suggesting that cells start utilizing different energy sources as an alternative under these conditions. Using this information, we are working on identifying lipid-related pathways that derive the growth and lipid production as a response to nutrient stress.


Microplastics in the Great Lakes

Abigail Snyder, Joseph A. Gardella, Sherri A. Mason and Angelina Montes

University at Buffalo, Department of Chemistry

Microplastics are a growing interest in the world of environmental science and are becoming more well-known as a component of plastic pollution. As the largest source of surface fresh water in the world, the Great Lakes are an important place to study the potential of these particles becoming pollutants and a transport medium of further pollution, specifically if they are also adsorbing potentially toxic chemicals to their surfaces. The goal of this research is to use surface analytical techniques like Fourier-transform infrared spectroscopy (FTIR) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) to characterize and examine the surfaces of microplastics taken from the Great Lakes for evidence of adsorbed chemical pollutants. Based on the data collected from our experiments and previous studies on the chemical relationships between plastics and pollutants in water, we concluded that chemicals such as Silicones(TM) and fluorocarbons are adsorbing to the surfaces of these microplastics due to the hydrophobicity of both the plastics and the chemicals of interest.


Toward Chemical Assembly of Split Toxins for Targeted Cancer Therapy

Hsuan-yi Wu, Yulin Tian and Qing Lin

University at Buffalo, Department of Chemistry

Diphtheria toxin (DT) and Pseudomonas aeruginosa exotoxin A (PE) are two bacterial toxins that have been employed in the design of the immunotoxin-based cancer therapies. These two toxins exhibit potent cell killing through enzymatic inactivation of the elongation factor 2 (EF-2), an indispensable protein component of the eukaryotic translational machinery. A number of immunotoxins have entered into clinical trials for treatment of a variety of cancers, including leukemia, breast cancer, and esophageal cancer. The structure of bacterial toxins are comprised of a catalytic domain, a translocation domain, and a receptor binding domain, though the order of linkage of these three domains may vary. A drawback of current immunotoxins is that due to their long half-lives in blood stream (usually two to three weeks), they can be potentially taken up by normal cells, leading to serious side effects. To overcome this problem, we hypothesized that the half-lives of immunotoxins can be significantly attenuated if we chemically assemble the immunotoxins selectively in cancer tissues in situ from the smaller protein domains. In this talk, I will describe our preliminary work in recombinant expression of the individual domains of the bacterial toxins, their conjugation to prostate cancer-targeting ligands, and the evaluation of the cell-killing activity of the cancer-targeted toxins in prostate cancer cell lines, PC3 and LNCaP


Quantitation of Stercobilin in the Fecal Material of Timothy Syndrome Mice as a Putative Biomarker for Autism

Emily Sekera Troy D. Wood, Heather L Rudolph and Stephen Carro

 University at Buffalo, Department of Chemistry

Autism Spectrum Disorders (ASD) is a general term for a group of complex disorders that currently effect 1 out of every 68 children in the United States which has risen significantly since 2007 (up from 1 out of every 150 children). Previous research in our group showed the depletion of an unknown in the urine of autistic children versus that of the controls. Utilizing MS/MS and FT-ICR MS the peak was determined to be the metabolite stercobilin. In this study, we utilize a highly-controlled animal model using transgenic Timothy Syndrome (TS) mice to determine if stercobilin is a viable biomarker for diagnosing autism. A method to create labelled stercobilin isotopomers for quantitation by mass spectrometry was developed and fine-tuned to test the fecal material from transgenic mice and their littermates. In the progress of our studies, we recognized that a higher yield of stercobilin than previously anticipated (based on stercobilin in urine) has been attained from the excrement samples. Due to this, response factor (RF) calculations were completed to determine the amount of spike that was necessary to quantify the amount of stercobilin in all of our samples. From here we aim to further evaluate the statistical significance of the depletion of stercobilin in “autistic” mice as a potential approach to diagnosing autism.