Sriya Chitti–Carbenoid-Boronate Building Blocks Enable Iterative Assembly of Saturated Small molecules

Abstract: “The building block-based approach is increasingly being recognized as a highly flexible and efficient method for the automated construction of molecules. For biomolecules such as polypeptides, oligosaccharides, and oligonucleotides the common linkages between building blocks is easy to recognize. This has led to the development of automated platforms which have broadly enabled both experts and non-experts to explore biomolecule chemistry. If a similar strategy could be applied to small organic molecules, the societal impact would be tremendous as it would address a key bottleneck in the development and discovery of new drugs, fragrances, fertilizers, and materials. Toward the objective of creating a building block-based platform for small molecule synthesis, we have developed a novel method of forming carbon-carbon bonds in near perfect selectivity using carbenoid-boronate building blocks. We are now demonstrating how the saturated and unsaturated portions of small molecules can be installed using this platform, thereby paving the way to the automated construction of small molecules. To further demonstrate the utility of our new method, we plan to complete the synthesis of a natural product, sch 725674, an antifungal macrolide.”

ECI 2020 Talk Transcript

Guo-Hsuen Lo–Engineering a photosynthetic yeast through endosymbiosis

Abstract: “Plants and algae conduct photosynthesis through chloroplasts, organelles descended from ancient endosymbiotic cyanobacteria. Despite the fundamental importance of endosymbiosis to the evolution of the eukaryotic cell, we have little practical understanding of how a bacterium was converted into an organelle. I am investigating the early stages of this endosymbiotic event in a laboratory setting by engineering eukaryote/prokaryote chimeras. This can be done by fusing a genetically tractable cyanobacterium with a model yeast cell to generate an endosymbiotic cyanobacterium which can survive and divide within the yeast cytosol. In this system, an auxotrophic cyanobacterium is inserted into a respiration-deficient yeast cell where it provides ATP and/or assimilated carbon (e.g. glucose) generated by photosynthesis. In return, the yeast cytosol provides an essential metabolite to the cyanobacterium. We have observed that mutant cyanobacteria can survive within yeast for multiple generations and can be engineered to enhance growth and longevity of the chimeras. I envision that the existing model may be further optimized to perform many downstream functions, including i) secretion of photosynthetic end-products, ii) host/symbiont protein exchange and iii) genome minimization and evolutionary studies.”

Engineering a photosynthetic yeast through endosymbiosis – transcript

Juan Canchola–Synthesis and Biological Evaluation of the Anaephene Natural Products

Abstract: “When antibiotics were introduced in the early twentieth century, they were very effective in treating bacterial infections. However, due to bacterial evolution, misuse and overreliance, these primary antibiotics are becoming less effective. Antibiotic resistance is becoming a major global issue, forcing us to question the stability of our pathogenic defenses. Natural products play a critical role in the development of new antibiotics and provide molecular templates for developing novel classes. Anaephenes A, B, and C are series of alkylphenols, that have shown to be effective antibiotics against Bacillus cereus and Staphylococcus aureus. They were isolated from a marine bacterium off the coast of Guam, known as Hormoscilla oscillatoriales. We have successfully synthesized anaephenes A and B, both which have never been synthesized before. We have confirmed the structure of these molecules using spectroscopic techniques such as 1H and 13C NMR, HMBC, HSQC, and COSY spectra. We have also confirmed their biological activity. Additionally, Anaephenes A and B displayed antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 16 and 8 ug/mL, respectively.”

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Huguette Clemente–Effects of Terpenoids (Thymoquinone and D-Carvone) on Protein Tyrosine Phosphatase 1β (PTP1β)

Abstract: “Protein tyrosine phosphatase-1β (PTP1β) is responsible for the negative regulation of insulin signaling and a therapeutic target for diabetes, cancer, and inflammation. Tremendous growth has been made in finding PTP1β inhibitors that comes from natural sources and exploring PTP1β regulatory mechanisms. The goal of our research is to see if thymoquinone, thymol, D-carvone, and carvacrol inhibit the enzyme protein tyrosine phosphatase-1β (PTP1β). Thymoquinone is a monoterpenoid and has been used as a drug for many things in recent history such as asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness and influenza. Thymol is a monoterpenoid phenol and is an isomer of carvacrol, it is currently not used as a drug, as an antiseptic and is present in some essential oils. Carvacrol is a monoterpenoid phenol which also has not been used as a drug before and, is currently used in perfumes and foods for its strong oregano smell and taste. Carvone is a terpenoid that has D and L enantiomers which have very different reactivity. In our research, we are using the D enantiomer which has been used for digestive drugs in humans and animals. The results from the inhibition of thymoquinone and D-carvone will be presented.”

Cody Busch–Antimicrobial properties of silver nanoparticle-impregnated wheat gluten biofilms

Abstract: “Wheat gluten (WG) biofilms result in a more affordable and biodegradable alternative for medical first aid bandages. WG biofilms were prepared by denaturing the WG protein with acid and heat, mixing with glycerol, and then drying to remove excess liquid. WG film properties such as density and porosity were measured. Different concentrations of silver nanoparticles (AgNPs) were synthesized and incorporated into the WG films to test their antimicrobial properties using several different pathogens. It was concluded that as the concentration of silver decreases, the diameter of the zone of inhibition also decreases, conveying that higher amounts of silver exhibit stronger antimicrobial properties. Incorporation of silver nanoparticles into WG biofilms had weaker antimicrobial properties than the silver disks alone. Some pathogens such as Klebsiella pneumoniae were more susceptible to the antimicrobial properties of WG with 0% AgNPs than WG with 100% AgNPs.”

ECI Abstract Manuscript

Namuunzul Otgontseren–Accessing In Vivo and Multiplexed Imaging through the Development of a Multicolor Panel of Activatable HNO Probes

Abstract: “Nitroxyl (HNO) is the one-electron reduced form of nitric oxide, a compound whose high reactivity makes it difficult to study. Previously, we developed NitroxylFluor, a fluorescent probe suitable for live-cell fluorescence imaging of HNO. This project aims to create derivatives of NitroxylFluor to optimize its localization, spectral properties, and photophysical properties. The proposed three congeners will be red-shifted as we replace the endocyclic oxygen of the xanthene chromophore with a quaternary carbon, dimethylsilicon, and a sulfonyl group. These probes will allow for multiplexed imaging with other probes, fluorescent proteins, or other labels to see interaction between HNO and other analytes and targets. With longer wavelength emissions from these derivatives, there will be reduced light scattering allowing deeper tissue penetration for in vivo imaging. With organelle directing groups, these probes will also give us a greater understanding of where HNO is produced at the subcellular level.”

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Connor Glenn–The Syntheses of Heteroatom-Activated Antibiotics

Abstract: “Since their discovery and subsequent proliferation in the 1920s, β-lactam antibiotics have contributed to the 50% increase in life expectance over the last century. However, antibiotic overuse and misuse, coupled with the rise in antibiotic resistant pathogens have caused the effectiveness of these drugs to decrease. Oxamazins are a class of heteroatom-activated β-lactam antibiotics that show good broad-spectrum antibiotic. The goal of our research is to progress through a traditional synthesis of simple oxamazins from readily available amino acids. We hope to explore the use of various synthetic strategies to make fully elaborated antibiotic compounds.”

Niya Mitchell–Design and Modeling of Macrocyclic RNA Targeting Agents for DM1

Abstract: “Myotonic-Dystrophy Type 1 (DM1) is a disease caused by the sequestration of splicing proteins, such as muscleblind-like 1 (MBNL1). The goal of this project is to find molecules that bind to RNA and inhibit MBNL protein sequestration. We used Myotonic-Dystrophy Type 1 (DM1) as a model system. I modeled a series of macrocyclic ligands in Molecular Operating Environment (MOE) using melamine or diaminopurine as a U-U mismatch recognition unit to target r(CUG)exp. The linker length of the ligands was varied to create stable macrocycles with promising hydrogen bonding. The results of these simulations can be coupled with experimental data to better our understanding of DM1 and ligand-RNA interactions.”

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Carolyn Oh–Optimizing and increasing throughput of capillary electrophoresis-electrospray ionization-mass spectrometry for single cell analysis of rat neurons

Abstract: “Single cell analysis is fundamental in understanding the behavior and physiology of organisms. Aplysia californica (A. californica) is a well-studied organism in learning and memory due to its simple nervous system and large neuron sizes. Previous analyses have successfully detected and quantified 20 proteogenic amino acids and several neurotransmitters in sensory neurons from the pleural ganglia of A. californica. However, applying this to mammalian single cells has proven to be difficult since they have 10 to a thousand times smaller cell volumes compared to A. californica cells. Here, capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) was used due to its ability to analyze small sample volumes and identify metabolites in single rat cerebellar neurons. To apply this technique to mammalian neurons, a sample preparation protocol was optimized with a desalting step to increase analyte signal intensities by using microfluidic separations coupled to ESI-MS. This new approach enables a tenfold increase in sample analysis rate to 2 minutes per analysis, allowing for high-throughput CE-ESI-MS experiments compared to a laboratory operated system. Using the microfluidic system, we successfully detected lysine, histidine, arginine, tyramine, and dopamine, thus expanding upon previous work by developing a protocol for rat neuron analysis. Future plans include applying the developed procedure to single neurons in different regions of the rat brain.”

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Nina Fatuzzo–Distal Alkenyl C-H Activation via Palladium/Norbornene Cooperative Catalysis

Abstract: “This project describes a site-selective functionalization of an alkenyl C-H bond using a modified Catellani reaction. The Catellani reaction, catalyzed by palladium and norbornene, traditionally results in both ortho and ipso functionalization of an aromatic ring. However, the corresponding alkenyl C-H functionalization via Pd/norbornene dual catalysis remains rare. On the other hand, Pd(II)-catalyzed directed C-H activation is well established through the formation of a palladacycle intermediate. This strategy relies heavily on substrate design and typically only activates the proximal C-H bond. In order to mediate these limitations, we report a catalyst-controlled distal alkenyl C-H functionalization. The reaction conditions are fairly mild and the time span of the reaction is only twelve hours. A variety of functional groups were shown to be compatible with the reaction conditions. In addition, both cyclic and linear alkenes reacted to form the desired product in a high yield. Mechanistic studies demonstrated that the reaction mechanism is consistent with that of the proposed Catellani reaction. Ultimately, the reported reaction is one of the first reactions in which the Catellani reaction can be applied to an alkenyl C-H bond to result in a distal C-H bond functionalization, providing a new and elegant synthetic tool.”

Text Transcript_Fatuzzo