Browsing Faculty Research and Publications by Title
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- Item1,5-(4,4'-Dipyridyl)naphthalene(MDPI, 2015) Hassan, Mohammad R.; Boeré, René T.The title compound has been prepared from 1,5-dibromonaphthalene (obtained from 1,5-diaminonaphthalene) using Suzuki-Miyaura cross-coupling to 4-pyridylboronic acid. The crystal and molecular structure was determined by single-crystal X-ray diffraction.
- Item1-methyl-4-thiocarbamoylpyridin-1-ium iodide(International Union of Crystallography, 2018) Shotonwa, Ibukun O.; Boeré, René T.In the title compound, C7H9N2S+·I−, the thioamide moiety is twisted out of the aromatic plane by 38.98 (4)° and forms N—H...I hydrogen bonds. In the crystal, hydrogen-bonded centrosymmetric dimers [C7H9N2S+·I−]2 are linked via additional short contacts from an aromatic CH group to the iodide anion into ribbons parallel to the (010) plane.
- Item2D analysis of polydisperse core-shell nanoparticles using analytical ultracentrifugation(Royal Society of Chemistry, 2017) Walter, Johannes; Gorbet, Gary E.; Akdas, Tugce; Segets, Doris; Demeler, Borries; Peukert, WolfgangAccurate knowledge of the size, density and composition of nanoparticles (NPs) is of major importance for their applications. In this work the hydrodynamic characterization of polydisperse core–shell NPs by means of analytical ultracentrifugation (AUC) is addressed. AUC is one of the most accurate techniques for the characterization of NPs in the liquid phase because it can resolve particle size distributions (PSDs) with unrivaled resolution and detail. Small NPs have to be considered as core–shell systems when dispersed in a liquid since a solvation layer and a stabilizer shell will significantly contribute to the particle's hydrodynamic diameter and effective density. AUC measures the sedimentation and diffusion transport of the analytes, which are affected by the core–shell compositional properties. This work demonstrates that polydisperse and thus widely distributed NPs pose significant challenges for current state-of-the-art data evaluation methods. The existing methods either have insufficient resolution or do not correctly reproduce the core–shell properties. First, we investigate the performance of different data evaluation models by means of simulated data. Then, we propose a new methodology to address the core–shell properties of NPs. This method is based on the parametrically constrained spectrum analysis and offers complete access to the size and effective density of polydisperse NPs. Our study is complemented using experimental data derived for ZnO and CuInS2 NPs, which do not have a monodisperse PSD. For the first time, the size and effective density of such structures could be resolved with high resolution by means of a two-dimensional AUC analysis approach.
- Item(2R,3aR,4S,7R,7aS,9R,10aR,11S,14R,14aS)-rel-3a,4,7,7a,10a,11,14,14aOctahydro-4,14:7,11-diepoxy-2,9propanonaphtho[1,2-f:5,6-f000]diisoindole1,3,8,10-tetrone (9CI): a cyclophane derived from naphtho[1,2-c:5,6-c]difuran(International Union of Crystallography, 2008) Thibault, Michelle E.; Parvez, Masood; Dibble, Peter W.The title compound, C25H18N2O6, is a naphthalenophane styled in the manner of Warrener's alicyclic cyclophanes or molecular racks wherein a trimethylene tether is perfectly staggered between the two N atoms such that the central methylene H atoms point toward the naphthalene [pi]-system. The dihedral angle between the mean planes of the two benzene rings is 7.61 (7)°.
- Item3,5-diphenyl-1,2,4-dithiazolium tetrabromidoferrate(III)(International Union of Crystallography, 2013) Shotonwa, Ibukun O.; Boeré, René T.
- Item3,7-Di-tert-butyl-1,5,2,4,6,8-dithiatetrazocine(International Union of Crystallography, 1995) Parvez, Masood; Boeré, René T.; Derrick, Sean; Moock, Klaus H.The eight-membered ring in the title compound, C10HI8N4S2, lies about an inversion centre and is essentially planar with normal bond lengths and angles [mean C--S 1.569 (2) and mean C--N 1.326 (3)A].
- Item4-methyl-N'-(2,2,2-trichloroethanimidoyl)benzene-1-carboximidamide(International Union of Crystallography, 2011) Roemmele, Tracey L.; Boeré, René T.
- ItemAdenine versus guanine DNA adducts of aristolochic acids: role of the carcinogen-purine linkage in the differential global genomic repair propensity(Oxford University Press, 2015) Kathuria, Preetleen; Sharma, Purshotam; Wetmore, Stacey D.Computational modeling is employed to provide a plausible structural explanation for the experimentally-observed differential global genome repair (GGR) propensity of the ALII-N2-dG and ALIIN6- dA DNA adducts of aristolochic acid II. Our modeling studies suggest that an intrinsic twist at the carcinogen–purine linkage of ALII-N2-dG induces lesion site structural perturbations and conformational heterogeneity of damaged DNA. These structural characteristics correlate with the relative repair propensities of AA-adducts, where GGR recognition occurs for ALII-N2-dG, but is evaded for intrinsically planar ALII-N6-dA that minimally distorts DNA and restricts the conformational flexibility of the damaged duplex. The present analysis on the ALII adduct model systems will inspire future experimental studies on these adducts, and thereby may extend the list of structural factors that directly correlate with the propensity for GGR recognition.
- ItemApplications and limitations of regulatory RNA elements in synthetic biology and biotechnology(Wiley, 2019) Nshogozabahizi, J. C.; Aubrey, K. L.; Ross, J. A.; Thakor, NehalSynthetic biology requires the design and implementation of novel enzymes, genetic circuits or even entire cells, which can be controlled by the user. RNA‐based regulatory elements have many important functional properties in this regard, such as their modular nature and their ability to respond to specific external stimuli. These properties have led to the widespread exploration of their use as gene regulation devices in synthetic biology. In this review, we focus on two major types of RNA elements: riboswitches and RNA thermometers (RNATs). We describe their general structure and function, before discussing their potential uses in synthetic biology (e.g. in the production of biofuels and biodegradable plastics). We also discuss their limitations, and novel strategies to implement RNA‐based regulatory devices in biotechnological applications. We close with a description of some common model organisms used in synthetic biology, with a focus on the current applications and limitations of RNA‐based regulation.
- ItemArchael proteins Nop10 and Gar1 increase the catalytic activity of Cbf5 in pseudouridylating tRNA(Nature Publishing Group, 2012) Kamalampeta, Rajashekhar; Wieden-Kothe, UteCbf5 is a pseudouridine synthase that usually acts in a guide RNA-dependent manner as part of H/ACA small ribonucleoproteins; however archaeal Cbf5 can also act independently of guide RNA in modifying uridine 55 in tRNA. This guide-independent activity of Cbf5 is enhanced by proteins Nop10 and Gar1 which are also found in H/ACA small ribonucleoproteins. Here, we analyzed the specific contribution of Nop10 and Gar1 for Cbf5-catalyzed pseudouridylation of tRNA. Interestingly, both Nop10 and Gar1 not only increase Cbf5’s affinity for tRNA, but they also directly enhance Cbf5’s catalytic activity by increasing the kcat of the reaction. In contrast to the guide RNA-dependent reaction, Gar1 is not involved in product release after tRNA modification. These results in conjunction with structural information suggest that Nop10 and Gar1 stabilize Cbf5 in its active conformation; we hypothesize that this might also be true for guide-RNA dependent pseudouridine formation by Cbf5.
- ItemAn arginine-aspartate network in the active site of bacterial TruB is critical for catalyzing pseudouridine formation(Oxford University Press, 2014) Friedt, Jenna; Leavens, Fern M. V.; Mercier, Evan; Wieden, Hans-Joachim; Wieden-Kothe, UtePseudouridine synthases introduce the most common RNA modification and likely use the same catalytic mechanism. Besides a catalytic aspartate residue, the contributions of other residues for catalysis of pseudouridine formation are poorly understood. Here, we have tested the role of a conserved basic residue in the active site for catalysis using the bacterial pseudouridine synthase TruB targeting U55 in tRNAs. Substitution of arginine 181 with lysine results in a 2500-fold reduction of TruB’s catalytic rate without affecting tRNA binding. Furthermore, we analyzed the function of a second-shell aspartate residue (D90) that is conserved in all TruB enzymes and interacts with C56 of tRNA. Site-directed mutagenesis, biochemical and kinetic studies reveal that this residue is not critical for substrate binding but influences catalysis significantly as replacement of D90 with glutamate or asparagine reduces the catalytic rate 30- and 50-fold, respectively. In agreement with molecular dynamics simulations of TruB wild type and TruB D90N, we propose an electrostatic network composed of the catalytic aspartate (D48), R181 and D90 that is important for catalysis by finetuning the D48-R181 interaction. Conserved, negatively charged residues similar to D90 are found in a number of pseudouridine synthases, suggesting that this might be a general mechanism.
- ItemAspheric solute ions moderate gold nanoparticle interactions in an aqueous solution: an optimal way to reversibly concentrate functionalized nanoparticles(American Chemical Society, 2015) Villarreal, Oscar D.; Chen, Liao Y.; Whetten, Robert L.; Demeler, BorriesNanometer-sized gold particles (AuNPs) are of peculiar interest because their behaviors in an aqueous solution are sensitive to changes in environmental factors including the size and shape of the solute ions. In order to determine these important characteristics, we performed all-atom molecular dynamics simulations on the icosahedral Au144 nanoparticles each coated with a homogeneous set of 60 thiolates (4-mercaptobenzoate, pMBA) in eight aqueous solutions having ions of varying sizes and shapes (Na+, K+, tetramethylamonium cation TMA+, tris-ammonium cation TRS+, Cl–, and OH–). For each solution, we computed the reversible work (potential of mean of force) to bring two nanoparticles together as a function of their separation distance. We found that the behavior of pMBA protected Au144 nanoparticles can be readily modulated by tuning their aqueous environmental factors (pH and solute ion combinations). We examined the atomistic details on how the sizes and shapes of solute ions quantitatively factor in the definitive characteristics of nanoparticle–environment and nanoparticle–nanoparticle interactions. We predict that tuning the concentrations of nonspherical composite ions such as TRS+ in an aqueous solution of AuNPs be an effective means to modulate the aggregation propensity desired in biomedical and other applications of small charged nanoparticles.
- ItemBackbone-substituted ß-ketoimines and ketoiminate clusters: transoid Li2O2 squares and D2-symmetric Li4O4 cubanes. Synthesis, crystallography and DFT calculations(MDPI, 2017) Gietz, Twyla M.; Boeré, René T.The preparation and crystal structures of four β-ketoimines with bulky aryl nitrogen substituents (2,6-diisopropylphenyl and 2,4,6-trimethylphenyl) and varying degrees of backbone methyl substitution are reported. Backbone substitution “pinches” the chelate ring. Deprotonation with n-butyllithium leads to dimeric Li2O2 clusters, as primary laddered units, with an open transoid geometry as shown by crystal structures of three examples. The coordination sphere of each lithium is completed by one tetrahydrofuran ligand. NMR spectra undertaken in either C6D6 or 1:1 C6D6/d8-THF show free THF in solution and the chemical shifts of ligand methyl groups experience signiﬁcant ring-shielding which can only occur from aryl rings on adjacent ligands. Both features point to conversion to higher-order aggregates when the THF concentration is reduced. Recrystallization of the materials from hydrocarbon solutions results in secondary laddering as tetramericLi4O4 clusters with a cuboidal core, three examples of which have been crystallographically characterised. These clusters are relatively insoluble and melt up to 250 ◦C; a consideration of the solid-state structures indicates that the clusters with 2,6-diisopropylphenyl substituents form very uniform ball-like molecular structures that will only be weakly solvated.
- ItemBiodefense implications of new-world hantaviruses(Frontiers Media, 2020) D'Souza, Michael H.; Patel, Trushar R.Hantaviruses, part of the Bunyaviridae family, are a genus of negative-sense, single-stranded RNA viruses that cause two major diseases: New-World Hantavirus Cardiopulmonary Syndrome and Old-World Hemorrhagic Fever with Renal Syndrome. Hantaviruses generally are found worldwide with each disease corresponding to their respective hemispheres. New-World Hantaviruses spread by specific rodent-host reservoirs and are categorized as emerging viruses that pose a threat to global health and security due to their high mortality rate and ease of transmission. Incidentally, reports of Hantavirus categorization as a bioweapon are often contradicted as both US National Institute of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention refer to them as Category A and C bioagents respectively, each retaining qualitative levels of importance and severity. Concerns of Hantavirus being engineered into a novel bioagent has been thwarted by Hantaviruses being difficult to culture, isolate, and purify limiting its ability to be weaponized. However, the natural properties of Hantaviruses pose a threat that can be exploited by conventional and unconventional forces. This review seeks to clarify the categorization of Hantaviruses as a bioweapon, whilst defining the practicality of employing New-World Hantaviruses and their effect on armies, infrastructure, and civilian targets.
- ItemBioinformatic analysis of structure and function of LIM domains of human zyxin family proteins(MDPI, 2021) Siddiqui, M. Quadir; Badmalia, Maulik D.; Patel, Trushar R.Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions.