The 8th Annual Chemistry Research Symposium
The 8th Annual Chemistry Research Symposium (CRS) will be held in the French Family Science Center on Monday, October 16, 2023, from 9:00 am and onwards. There will be keynote speakers, talks from current graduate students, poster presentations, a continental breakfast and catered lunch, and more! This is a great way to learn about research going on in other labs around the department and—if you’re new—to get a good feel for the Duke Chem culture as you embark on your graduate career.
Registration for this event has closed. See you on Monday!
|9:00 AM||Breakfast | Atrium|
|9:45 AM||Welcome | Bonk Lecture Hall|
|10:00 AM||Session 1 | Bonk|
|10:30 AM||Lightning Session | Bonk|
|10:45 AM||Break | Atrium|
|11:00 AM||Keynote: Dr. Julie Pollock | Bonk|
|12:00 PM||Lunch | 2237|
|1:00 PM||Session 2 | Bonk|
|1:45 PM||Break | Atrium|
|2:15 PM||Session 3 | Bonk|
|3:00 PM||Break | Atrium|
|3:15 PM||Keynote: Dr. Olivier Delaire | Bonk|
|4:30 PM||Poster Session | FFSC 1st Floor|
Yiquan Zhao | Skyler Cochrane
Loren Smith | Morgan Bailey | Emily Swanson
Aaron Keeler | Max McWhorter | Finn Tran
Presentation titles and abstracts
Dr. Julie Pollock: “The Power of Collaborative, Interdisciplinary Research: Strategies Towards the Development of Selective Drug-like Molecules”
My chemical biology research laboratory at the University of Richmond focuses on understanding, detecting, and combating human diseases such as cancer and inflammation from an interdisciplinary approach leveraging collaborations both on- and off-campus. This seminar will focus on my scientific and personal journey highlighting two recent approaches from the group on the development of selective prodrugs. Prodrugs have been utilized to optimize drug properties and decrease off-target effects for decades. These inactive derivatives undergo an enzymatic or chemical transformation within a biological environment to release the active parent drug and exert the desired effects. Specifically we have focused on the development of two types of prodrugs: hydrogen peroxide activated estrogen receptor ligands and photoactivated ruthenium-based chemotherapies. We have masked an estrogen receptor beta selective agonist as a boronic ester which is released selectively using pathological levels of hydrogen peroxide found in neurodegenerative diseases. In addition, we have evaluated ruthenium-based complexes and the byproducts generated through photodissociation as potential anticancer drugs.
Lab Website: https://blog.richmond.edu/pollocklab/
Julie Pollock earned her PhD from the McCafferty Lab at Duke University in 2011. Following her time as a blue devil she completed a postdoc at the University of Illinois Urbana-Champaign as a recipient of the NIH Postdoctoral Fellowship in Endocrine, Developmental, and Reproductive Toxicology. Dr. Pollock became a faculty member at the University of Richmond in 2014 where she remains today as an associate professor of chemistry and biochemistry. It’s there that Dr. Pollock has provided undergraduate researchers the necessary tools to probe important questions pertaining to breast cancer and inflammatory disease using chemical biology techniques, biochemical methods, and organic synthesis. The Pollock Lab is primarily focused on using chemical biology approaches to understand disease development and progression.
Dr. Olivier Delaire: “Atomistic energy conversion processes in materials for sustainable energy: studies with neutrons, x-rays and computer simulations“
Determining the dynamics of atoms in materials is critical to surmount bottlenecks toward efficient energy conversion and sustainable energy technologies. For instance, understanding the ionic diffusion processes is key in the design of solid-state electrolytes for future solid-state batteries and improved fuel-cells [1,2,3]. Ionic vibrations in crystals are also central to understand and manage heat conduction and thermal properties in solids [4,5,6], and the electron-phonon coupling that underlies thermalization of photocarriers in photovoltaics . Yet, classic models of atomic motions in solids are insufficient for the rational design of improved energy materials. This talk will highlight recent method developments and progress in probing and rationalizing the complex microscopic dynamics of materials, and the quest to reach next-level understanding and predictive theoretical models for improved energy efficiency.
The Delaire group uses state-of-the-art neutron and x-ray scattering techniques at large user facilities, providing extensive datasets. We also perform first-principles simulations to achieve a quantitative correspondence with experiments, for instance based on ab-initio molecular dynamics augmented with machine learning techniques. Combined, these methods allow us to identify underlying principles and descriptors for the design of future materials.
This presentation will highlight exciting science performed at Duke and many DOE national labs, using complementary experimental and computational modalities, echoing the speaker’s career path. We will discuss how superionic crystals can reach ionic diffusivities rivaling those of liquid electrolytes, enabling safer and more energy-dense solid-state batteries. We will also consider how ‘floppy’ crystal structures like halide perovskites exhibit large-amplitude atomic fluctuations that can lead one to question traditional crystallographic views and call for new theoretical treatments of their electronic structure at operating temperatures.
 M. Gupta, et al. “Fast Na diffusion and anharmonic phonon dynamics in superionic Na3PS4”, Energy and Environ. Science (2022)
 J. Ding, et al. “Anharmonic lattice dynamics and superionic transition in AgCrSe2”, PNAS (2020).
 J. Ding et al. “Non-Debye behavior and overdamped normal modes reveal liquid-like dynamics in solid-state Li electrolyte” (2023)
 J. Ding et al. “Anharmonic phonons and origin of ultralow thermal conductivity in Mg3Sb2 and Mg3Bi2”, Science Advances (2021)
 T. Lanigan-Atkins*, S. Yang* et al. “Extended anharmonic collapse of phonon dispersions in SnS and SnSe”, Nature Commun (2020).
 Q. Ren, et al. “Extreme phonon anharmonicity underpins superionic diffusion and ultralow thermal conductivity in argyrodite Ag8SnSe6”, Nature Materials (2023)
 T. Lanigan-Atkins*, X. He* et al. “Two-dimensional overdamped fluctuations of soft perovskite lattice in CsPbBr3”, Nature Materials 20, 977-983 (2021)
Lab Website: delaire.pratt.duke.edu
Olivier Delaire obtained his PhD in Materials Science from Caltech (2006). He joined Oak Ridge National Laboratory as a Clifford Shull Fellow in the Neutron Sciences Directorate (2008), later becoming Staff Researcher in the Materials Science and Technology Division (2012). In 2016, he became Associate Professor in the Thomas Lord Department of Mechanical Engineering and Materials Science at Duke University, with secondary appointments in the Physics and Chemistry departments. The Delaire group at Duke carries research at the interface of materials science, condensed matter physics and solid-state chemistry, with an emphasis on atomic dynamics. For instance, we investigate phonons in crystals and their interactions with electron or spin degrees-of-freedom, as well as ionic diffusion and phase transitions.
Yiquan Zhao: “Synthesis of Daucane-Type Natural Products with Antiausterity Activity against the PANC-1 Pancreatic Cancer Cells”
Human pancreatic cancer has become the seventh leading cause of cancer-related death worldwide. However, current first-line chemotherapeutic agents only offered limited increase in median survival rates, and development of new treatment strategies is necessary. Considering that the pancreatic cancer cells are under constant nutrient deprivation, which may contribute to their genomic instability and drug resistance, compounds that target tolerance of pancreatic cancer cells to nutrient starvation conditions provide an excellent starting point for drug discovery. In 2020, two daucane-type sesquiterpenoids were determined to possess promising antiausterity activity against the PANC-1 human pancreatic cancer cell line. Therefore, the goal of our research is to complete the first total synthesis of both compounds.
Our synthetic strategy utilizes a divergent approach, in which the two structurally similar compounds will be obtained via a common intermediate with minimal variations in steps. Starting from commercially available (S)-epichlorohydrin, we have completed the synthesis of the first compound and reached the last stage in preparing the second compound. Our synthesis features a silicon-tethered tandem radical cyclization-trapping strategy to achieve an efficient, stereoselective installation of substituents on the five-membered ring system. Upon completion of the syntheses, analogs of the target compounds will be designed and synthesized, and structure-activity relationships (SARs) will be established to guide future development of antiausterity agents to treat human pancreatic cancer.
Skyler Cochrane: “Structure-activity relationship (SAR) of novel antibiotics targeting LpxH in lipid A biosynthesis”
The emergence of multidrug-resistant nosocomial Gram-negative (GN) pathogens has become a major public health threat. Carbapenem-resistant P. aeruginosa, A. baumannii, and extended-spectrum-ï¢-lactamase (ESBL)-producing Enterobacteriaceae are the top three pathogens that pose the greatest threat to human health in the 2017 WHO report. This alarming list highlights the urgent need to develop new antibiotics, preferably by targeting novel pathways in these bacteria, for which existing resistance mechanisms are lacking. GN bacteria are characterized by enrichment of lipid A-anchored LPS or LOS in the outer monolayer of their outer membrane. Lipid A biosynthesis represents a highly conserved pathway that has never been exploited by commercial antibiotics.
Targeted inhibition of the fourth step of lipid A biosynthesis, LpxH, has proven to be a promising route for antibiotic development. Accumulating evidence from our recent studies shows that inhibition of lipid A enzymes such as LpxH, kills bacteria not only by disrupting the essential lipid A biosynthesis, but also by accumulating toxic lipid A intermediates, thus delivering a double punch for bacteria. Our preliminary structural characterization of AZ1 in complex with LpxH has led to the development of more potent inhibitors. By conducting an in-depth structural analysis of LpxH in complex with several generations of AZ1-based inhibitors, we have not only gleaned vital knowledge about the electrostatic forces dictating inhibitor recognition of LpxH, but also developed a suitable candidate for in vivo trials that displays a good safety profile and has a preliminary rate of 80% in recovering mice from lethal infections of Klebsiella pneumoniae.
Loren Smith: “Eliminating Quadrupolar Degradation of SABRE Hyperpolarization”
Signal intensity in conventional NMR spectroscopy is weak. In the current largest clinical magnet, only 0.001% H are detected in a sample. Several “hyperpolarization” techniques have been developed to increase the proportion of detectable nuclei in a sample and thus enhance NMR signal intensity. Signal Amplification by Reversible Exchange (SABRE) is a promising technique that uses parahydrogen and an iridium polarization transfer catalyst to enhance the population of detectable nuclei by roughly 10,000-fold quickly and inexpensively on a variety of compounds. Currently, most SABRE experiments target the enhancement of N because the SABRE catalyst kinetically favors binding to nitrogen and N is a spin-Â½ nucleus that favors polarization build-up. However, the ability to hyperpolarize other spin-Â½ nuclei while retaining the kinetic benefits of a nitrogen-containing molecule would greatly expand the capabilities of SABRE. For example, just by targeting C as opposed to N, we may generate 2.5-times greater magnetization for the same spin polarization and concentration. C- N isotopes are cost-prohibitive for medical applications. SABRE hyperpolarization of C- N systems has not yet been possible because N has a quadrupolar moment with incredibly fast relaxation that inhibits polarization build-up. In this work, we introduce a computer-optimized multi-axial pulse sequence that can generate significant SABRE hyperpolarization in quadrupolar systems. We describe the algorithm used to generate the pulse sequence as well as the simulated performance of the sequence. We detail a new experimental set-up using water-cooled, 3D-printed coil sets to deliver multi-axial pulses at mT fields, and discuss experimental data obtained using this apparatus. This sequence represents an exciting advancement in the clinical viability of SABRE as it greatly expands the scope of chemical targets available to the technique.
Morgan Bailey: “Stability-based Proteomics for the Investigation of Structured RNA-protein Interactions”
RNA-protein interactions are essential to RNA function throughout biology. Identifying the protein interactions associated with a specific RNA, however, is currently hindered by the need for RNA labelling or costly tiling-based approaches. Conventional strategies, which commonly rely on affinity pull-down approaches, are also skewed to the detection of high affinity interactions and frequently miss weaker interactions that may be biologically important. Reported here is the first adaptation of stability-based mass spectrometry (MS) methods for the global analysis of RNA-protein interactions. The stability of proteins from rates of oxidation (SPROX) and thermal protein profiling (TPP) methods are used to identify the protein targets of three RNA ligands, the MALAT1 triple helix (TH), a viral stem loop (SL), and an unstructured RNA (PolyU) in LNCaP nuclear lysate. The 315 protein hits with RNA-induced conformational and stability changes detected by TPP and/or SPROX were enriched in previously annotated RNA-binding proteins and included new proteins for hypothesis generation. Also demonstrated is the orthogonality of the SPROX and TPP approaches, and the utility of the domain-specific information available with SPROX. This work establishes a novel platform for the global discovery and interrogation of RNA-protein interactions that is generalizable to numerous biological contexts and RNA targets.
Emily Swanson: “High-Throughput Screening of Triplex-Containing RNA Motifs Identifies Catechols as a Metal-Mediated Triplex Binding Motif”
Non-coding RNA is capable of folding into complex structures that form binding pockets similar to those in proteins. One such fold is a triple helix, or triplex, where a third strand of RNA binds in the groove of a double helix. This motif can be found across mammalian, viral and bacterial RNA molecules, and in the present study two mammalian and two viral RNAs were screened using the Duke RNA-Targeted Library (DRTL). From the screening two scaffolds were identified as unique triplex binding motifs, one being a dye-like scaffold and the other consisting of flavonoids. The flavonoids showed strong binding to all four RNAs, and structure activity relationship studies revealed key interactions between the molecule and RNA. Specifically, at least two neighboring hydroxyl groups were necessary for high-affinity binding to the triple helices. Through further studies, these interactions were found to be mediated by divalent cations. Although the exact identity of the metal is still unknown, future work aims to further elucidate the key metal(s) involved in catechol binding. Additionally, we are investigating the activity of these molecules in functional assays and further exploring scaffold diversification through scaffold hopping with the goal of identifying more selective catechol-containing ligands.
Aaron Keeler: “Characterizing Domain-Specific Probes of Plasmodium falciparum Heat Shock Protein 70-1 for use as Novel Therapeutics”
Malaria remains a significant disease that results in millions of infections and hundreds of thousands of deaths each year. Plasmodium falciparum, the causative agent of the large majority of all human malaria deaths, contains multiple biomachinery regulators of proteostasis termed heat shock proteins (Hsps) that facilitate proper protein folding and regulation. PfHsp70-1, has been shown to be essential in all life stages of P. falciparum however, we currently lack domain-specific chemical probes targeting PfHsp70-1, resulting in a lack of understanding of the molecular functions of this and other Hsp proteins throughout the Plasmodium lifecycle. Here, we perform a thermal shift assay high-throughput screen to identify prioritized small molecule binders of PfHsp70-1, characterize their effect on the activity of PfHsp70-1, and determine their binding affinity to PfHsp70-1. We find that compounds AMK3 and AMK4 showed low-micromolar binding affinity to PfHsp70-1 by microscale thermophoresis (MST) and exhibit high selectivity (>25-fold) for PfHsp70-1 over HsHsp70-1. A suite of proteomic methods was utilized to determine the binding locations of AMK3 and AMK4, and we show that AMK3 targets the N-terminal domain of PfHsp70-1 while AMK4 targets a previously unknown C-terminal binding site and disrupts peptide binding. A MD-facilitated structure activity relationship (SAR) screen was performed on AMK3, yielding a lead compound with similar efficacy, and greatly reduced cytotoxicity. This study identifies promising selective, domain-specific probes of PfHsp70-1 that may be useful starting points for therapeutic development. This work increases our knowledge of Hsp targeting in Plasmodium and furthers our ability to explore the role of individual PfHsp70-1 domains during infection.
Max McWhorter: “Prediction and Discovery of Photovoltaic Semiconductor Materials”
In order to address demand for low-cost, high efficiency, earth abundant photovoltaic semiconductors, we have developed a combined computational and experimental approach for the discovery of new multinary chalcogenide materials. To demonstrate the power of this method, we have begun to explore systems within the I2-II-IV-X4 and I2-I’-V-X4 chalcogenide families, and have already identified several promising candidates for photovoltaic application.
Finn Tran: “Using DFT simulations for co-ligand design to fine-tune the exchange rate of polarization targets in SABRE”
Magnetic resonance has various applications in chemistry and medicine. However, it is an insensitive technique where only around 3 protons out of 1,000,000 are detectable at a 1 T field at room temperature. Hyperpolerization techniques can enhance signal intensities by several magnitudes to overcome inadequate signal-to-noise ratio. Signal Amplification By Reversible Exchange (SABRE) is a novel technique using parahydrogen as a spin order source to polarize various spin-half nuclei including 1H, 13C, or 15N. SABRE relies on the reversible binding between the organometallic polarization transfer catalyst, the parahydrogen, and the polarization target. In this process, the exchange rate of the target ligand is crucial for optimizing the hyperpolarization efficiency. However, different ligands exchange at unique rates, which points to a need to tune them to the most optimal rate. Auxiliary ligands (co-ligands) have been used to expand the chemical scope of SABRE by inducing a more amenable exchange rate on the polarization target. We report a combined computational and experimental approach to predict how structurally analogous co-ligands alter the target ligand exchange rate and subsequently quantify that change. We find that the HOMO-LUMO gap predicted from DFT simulations correlates with the experimentally determined target ligand exchange rate when using pyridine and its derivatives as the co-ligand.
Jiaqi Zhu: “CuH-Catalyzed Reductive Coupling of Azatrienes and Ketones for the Synthesis of (Z)-Allylic 1,2-Amino Alcohols”
The stereoselective synthesis of 1,2-amino alcohols has been the focus of numerous synthetic efforts due to the abundance of the vicinal amino alcohol moiety in pharmacologically active compounds; among those, (Z)-allylic 1,2-amino alcohols are challenging building blocks. By using CuH-catalyzed hydrofunctionalization strategy on azatriene, we developed a new method for the synthesis of chiral (Z)-allylic 1,2-amino alcohols through a C–C bond formation that directly generates two stereogenic centers as well as selectively forms an internal (Z)-alkene.
Hassan Alkhunaizi: “Optimizing bridge fragment design for triplet energy transfer”
Triplet (Dexter) energy transfer (DET) describes the spin-forbidden transport of excitons that relies on exchange interactions between the energy donor (D) and acceptor (A) species. DET plays an important role in many light harvesting assemblies, such as solar cells. Unlike Forster energy transfer, DET does not depend on coulombic interactions among the D and A species, making the process merely dominant in short distances. To circumvent this challenge, I propose the design of a Dexter transport system that is made of D and A fragments, connected to a linker bridge (B) that is near-resonant in energy with the D fragment. This design will promote a ballistic exciton migration from D to B before getting trapped in the A fragment.
Grace Bertles: “Investigation of Metal-Induced Protein Precipitation Reactions across Multiple Proteomes “
Cu-induced protein aggregation has long been related to cellular dysfunction and cellular Cu-toxicity. The biophysical basis behind metal-induced protein aggregation and the relative susceptibility of cellular proteins to this effect remains poorly understood. Reported here is the susceptibility of proteins to precipitate upon addition of Cu, probed using a Metal-induced Protein Precipitation (MiPP) methodology. MiPP allows for the determination of Cm values for each identified protein (i.e., the concentration of Cu at which half the protein is precipitated). This ultimately enables a quantitative means to assess the sensitivity of proteins across proteomes to Cu precipitation. Subsequent analyses of the protein assayed by MiPP reveals biophysical properties that correlate with MiPP tolerant and sensitive proteins.
As part of this work proteins in an E. coli cell lysate were exposed to a range of Cu concentrations, insoluble protein aggregates were precipitated by centrifugation, and the remaining soluble protein in the samples at each Cu concentration was quantified using quantitative bottom-up proteomics experiment with isobaric mass tags and an LC-MS/MS readout. Subsequent bioinformatics analyses were performed to elucidate biophysical properties, such as amino acid content and secondary structure, tied to a protein’s sensitivity or tolerance to Cu-induced protein precipitation. In E. coli, unstructured regions were found to be more prevalent in MiPP tolerant proteins, while the alpha-helical regions were more prevalent in sensitive proteins compared to tolerant proteins. Ongoing work is focused on using the MiPP methodology established to study the behavior of proteins in yeast and mammalian cell lysates to help determine overarching properties responsible for MiPP sensitivity or tolerance (e.g., is MiPP sensitivity/tolerance an conserved property of proteins or is it driven by amino acid composition and/or secondary structure as observed in our E. coli results?).
Yin Mei Chan: “Enhancement of Schwann Cell Migration using Aligned Nanofiber Conduits for Peripheral Nerve Reconstruction”
Despite optimal peripheral nerve reconstruction for nerve defects, return of sensory and motor function is often slow and inconsistent. Current clinical techniques for peripheral nerve repair, including autologous nerve grafting, face many difficulties such as undesirable reliance on donor nerve availability, sacrifice of donor function, and size and structural compatibility, in critically-sized transection injuries (greater than 3 cm in humans). Consequently, a new methodology allowing for in-situ endogenous repair of the severed nerve would advance patient prognosis compared to autologous grafts. Key to the regenerative process are the behavior of Schwann cells (SCs) to impart biomolecular and topographical cues for regrowing axons. Axonal regeneration only proceeds to the extent of which SCs are able to migrate from the proximally intact nerve. To optimize SC migration, our lab has sought to develop synthetic nanofibrous scaffolds that provide affinity and guidance to enhance SC migration and subsequently, axonal outgrowth. SCs seeded on fibers exhibited elongated morphology when compared to plates without fibers, indicating enhanced migratory behaviors. Further migratory studies found that SCs specifically migrate in the x-axis (defined as the direction of aligned fibers) on a 2D scaffold in the presence of nanofibers. SCs on nanofibers moved at speeds of 0.24, 0.25, and 0.22 Âµm/min along the x-axis for diameters of 1.65, 1.18, and 0.87 Âµm respectively, demonstrating higher rates than that of SCs on no fibers (0.19 Âµm/min). Near-zero speeds were recorded for SC migration on nanofibers in the y-direction. As such, the use of synthetic, nanofibrous scaffolds improved the directionality and rate of migration of SCs in vitro. Efforts to implement such nanofibrous scaffolds during nerve reconstruction may enhance the efficiency and efficacy of nerve repair through directionally-guiding SCs in the immediate postoperative regenerative period.
Victoria Cinnater : “Synthesis and Photophysics of Highly Electron-Deficient Porphyrin Oligomers”
Herein, we report highly electron-deficient perfluoroalkyl porphyrin arrays, An, as a novel class of acceptor materials capable of driving a broader range of photo-oxidation reactions. These systems feature (1) impressive excited-state reduction potentials (A2 1E−/ *= 1.54 V; A3 1E−/ *= 1.50 V), (2) S0 to S1 transitions that gain intensity and progressively red-shift with increasing numbers of porphyrin units, and (3) nanosecond S1 lifetimes, suggesting their utility as powerful photo-oxidants. In this work, (perfluoroalkyl)porphyrin oligomers of varying lengths have been designed, synthesized, and characterized through a combination of photophysical and potentiometric experiments. Time-resolved pump-probe transient absorption (TA) experiments characterize their singlet charge transfer state lifetimes and S1-to-T1 state intersystem crossing dynamics. These studies, coupled with potentiometric data, provide a deeper understanding of rules and principles by which multi-porphyrin assemblies carry out photoinduced charge transport triggered by long-wavelength excitation.
Lucas Everhart: “Enhancing SABRE-SHEATH hyperpolarization using computer optimized multi-axial pulse shapes”
SABRE (signal amplification by reversible exchange) is a polarization method used in magnetic resonance experiments to increase the magnetization of a substrate. Nuclear spin order is transferred from parahydrogen (pH2) to a substrate’s target nucleus, generally a spin- ½ nuclei such as 1H, 13C, or 15N, by means of a spin coupling network and an organometallic catalyst. This hyperpolarization technique can greatly enhance the nuclear magnetic resonance response of a substrate, thereby increasing the intensity of spectral peaks and its performance in applications such as in vivo metabolic imaging. To improve upon the SABRE technique, we have built evolutionary strategy algorithms to optimize multi-axial RF-pulse shapes. These shapes are simulated using RogueSpin, a physically accurate SABRE hyperpolarization model built in house by the Warren Lab, then empirically tested once an arbitrary hyperpolarization threshold has been achieved. Here, we present two experimental systems: circularly polarized SABRE-SHEATH, a transverse irradiation method that demonstrates our group’s simulation-optimization-experimentation workflow; 13C-acetate SABRE, a current focus of our computer optimized, multi-axial pulse shaping efforts.
Kacey Godwin: “Design and investigation of poly(ester urea)s for biomedical applications”
As the field of medicine continues to progress, there is an increasing need for novel biodegradable materials. Many current FDA-approved medical devices are not easily broken down in the body which can lead to unwanted complications such as inflammation, and the need for repeated invasive operations. Therefore, it is integral to provide new materials that can be finely tuned in both their mechanical and physical properties. Poly(ester urea)s have been used in biomedicine for decades and are emerging as a promising candidate for addressing this gap. The generation of a material library can help further identify potential in vitro in vivo correlations (IVIVC) that allow us to map and predict expected degradation behavior from a small baseline dataset.
Hannah Switzer: “Using non-canonical amino acids to immobilize a hyperthermophilic enzyme and increase protein stability”
A carboxylesterase was immobilized onto an epoxy-activated sepharose resin using non-canonical amino acids. Immobilization yielded an enzyme displaying increased recyclability, heightened performance in organic solvents, and stability at room temperature for over two years. Thus, non-canonical amino acids could increase the utility of proteins in non-biological environments.
Gianna Tutoni: “Towards tunable, degradable, stereocomplexed hydrogel microparticles via microfluidic assembly”
Hydrogel microparticles (HMPs) have been heavily explored for tissue engineering and drug delivery due to their resemblance to native tissue and ease of biofunctionalization. However, translation of these highly tunable systems has been hindered by covalent crosslinking methods. While often employed acrylate moieties allow spatial-temporal control of crosslinking and functionalization, the strong C-C bonds formed prevent degradation/resorption and ultra-violet curing methods limits cellular encapsulation. Stereocomplexation, a stereospecific form of physical crosslinking, provides a strong yet degradable alternative for creating translationally relevant HMPs. For this system, gel network components consisting of 4-arm polyethylene glycol (PEG) stars with poly(L-lactic acid) oligomeric chain ends and propargyl-containing ABA crosslinkers with enantiomeric poly(D-lactic acid) chain ends were synthesized. Droplets of gel precursors in ethyl acetate were formed via a microfluidic organic-in-oil system where HMPs self-assemble after precipitation in deionized water. Gelation due to stereocomplexation was confirmed via wide angle x-ray scattering (WAXS) and differential scanning calorimetry (DSC). This HMP scaffold provides opportunity for biofunctionalization, mechanical/degradable tunability, and formation of microporous annealed scaffolds, showing great promise for future use in regenerative medicine technologies such as bioprinting.