A5082952838- Supramolecular Chemistry and Complexes
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Crystallography and molecular interactions
- RNA modifications and cancer
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Mosquito-borne diseases and control
- Virology and Viral Diseases
- Molecular Sensors and Ion Detection
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Chemical Synthesis and Analysis
- HIV Research and Treatment
- Cancer-related molecular mechanisms research
- Biochemical and Molecular Research
- Mechanical and Optical Resonators
- Luminescence and Fluorescent Materials
- Supramolecular Self-Assembly in Materials
- Advanced MEMS and NEMS Technologies
- Porphyrin and Phthalocyanine Chemistry
- Acoustic Wave Resonator Technologies
- Carbohydrate Chemistry and Synthesis
- Ultrasound and Cavitation Phenomena
San Diego State University
2015-2025
S.P.E.C.I.E.S.
2019
Global Viral
2019
University of San Diego
2016
University of Denver
2009-2014
University of Colorado Boulder
2009-2010
Institut Català d'Investigació Química
2008
Taras Shevchenko National University of Kyiv
2008
Institució Catalana de Recerca i Estudis Avançats
2008
Enamine (Ukraine)
2008
The nucleolus is the largest biomolecular condensate and facilitates transcription, processing, assembly of ribosomal RNA (rRNA). Although nucleolar function thought to require multiphase liquid-like properties, fluidity its connection highly coordinated transport biogenesis subunits are poorly understood. Here, we use quantitative imaging, mathematical modeling, pulse-chase nucleotide labeling examine material properties rRNA dynamics. mobility several orders magnitude slower than that...
Fluorescence imaging is a powerful method for probing macromolecular dynamics in biological systems; however, approaches cellular RNA are limited to the investigation of individual constructs or bulk labeling methods compatible primarily with fixed samples. Here, we develop platform fluorescence living cells. We show that fluorescent bicyclic and tricyclic cytidine analogues can be metabolically incorporated into by overexpression uridine–cytidine kinase 2. In particular, metabolic feeding...
Most fluorescent nucleoside analogues are quenched when base stacked and some maintain their brightness, but there has been little progress toward developing that markedly increase fluorescence upon duplex formation. Here, we report on the design synthesis of a new tricyclic cytidine analogue, 8-diethylamino-tC (8-DEA-tC), responds to DNA formation with up 20-fold in quantum yield as compared free nucleoside, depending neighboring bases. This turn-on response is greatest any reported...
We investigate the fluorescent pyrimidine analogue ABN in duplex DNA oligonucleotides, showing that is unique among nucleobase analogues enabling single-molecule fluorescence studies of oligonucleotides using standard equipment.
We report a host molecule with an inwardly directed methyl ester and its reaction series of tertiary amines. The product is complex the carboxylate guest quaternary ammonium salt. rate highly dependent on suitability amine to occupy cavity intrinsic reactivity resulting complex. A kinetic study 2-(dimethylamino)ethanol produce choline gives activation parameters DeltaH = 25.1 +/- 0.5 kcal mol-1 DeltaS 12 2 cal K-1. complex, once formed, poised reach transition state; acceleration greater...
We report that a synthetic, vase-shaped host molecule forms complexes with quinuclidine and accelerates the Menschutkin reaction in nanoenvironment provides. Kinetic simulation is used to determine rate constants for reactions of complex, these are compared control absence host. The efficacy effecting this supramolecular acceleration dependent on structures alkylating agent its leaving group.
The present research was undertaken to determine the conformations of alkyl groups that are forced into small spaces. Unbranched assume fully extended in free space solutions, because any bends structure create steric clashes between hydrogens along chain. We synthesized a series esters carboxylic acid attached inner surface vase-shaped container structure. shorter (ethyl and propyl) can be accommodated conformations, even solvent molecules share container’s space. Longer (butyl-octyl) adopt...
Fluorescent RNA is an important analytical tool in medical diagnostics, cytochemistry, and aptamer development. We have synthesized the fluorescent ribonucleotide analogue 1,3-diaza-2-oxophenothiazine-ribose-5'-triphosphate (tCTP) tested it as substrate for T7 polymerase transcription reactions, a convenient route generating vitro. When transcribing guanine, incorporates tCTP with 2-fold higher catalytic efficiency than CTP efficiently polymerizes additional NTPs onto tC. Remarkably, does...
We studied the incorporation of fluorescent cytidine analogues 1,3-diaza-2-oxophenothiazine (tC) and 1,3-diaza-2-oxophenoxazine (tCo) by human DNA polymerase alpha Klenow fragment I (Escherichia coli). These tricyclic nucleobases possess regular hydrogen bonding interface cytosine but are significantly expanded in size toward major groove. Despite alteration, both polymerases insert dtCTP dtCoTP with remarkable catalytic efficiency. Polymerization opposite guanine is comparable to insertion...
Pyrogallol[4]arene is a macrocycle with concave surface and 12 peripheral hydroxyl groups that mediate its self-assembly to form hexamers of octahedral symmetry in the solid state, solution, gas phase. These enclose approximately 1300 Å3 space, which filled small molecules. In this study, we show solvent-free conditions for guest entrapment these hexamers, using molten molecules as solvent allowing capsules assemble during cooling, results exceptionally kinetically stable encapsulation...
Zika virus (ZIKV) has been linked to the development of microcephaly in newborns, as well Guillain-Barré syndrome. There are currently no drugs available treat ZIKV infection, and accordingly, there is an unmet medical need for discovery new therapies.
Solvent matters: By carrying out the assembly of pyrogallolarene hexamers under thermal conditions in absence solvent, highly efficient loading guest molecules to produce kinetically trapped assemblies was achieved. Such products are not formed when solvents present (see schematic). Detailed facts importance specialist readers published as ”Supporting Information”. documents peer-reviewed, but copy-edited or typeset. They made available submitted by authors. Please note: The publisher is...
Abstract The rational design of fluorescent nucleoside analogues is greatly hampered by the lack a general method to predict their photophysics, problem that especially acute when base pairing and stacking change fluorescence. To better understand these effects, series tricyclic cytidine (tC tC O ) ranging from electron‐rich electron‐deficient was designed synthesized. They were then incorporated into oligonucleotides, photophysical responses studied. When inserted double‐stranded DNA...
Fluorescent nucleobase surrogates capable of Watson-Crick hydrogen bonding are essential probes nucleic acid structure and dynamics, but their limited brightness short absorption emission wavelengths have rendered them unsuitable for single-molecule detection. Aiming to improve on these properties, we designed a new tricyclic pyrimidine nucleoside analogue with push-pull conjugated system synthesized it in seven sequential steps. The resulting C-linked...
Abstract Tricyclic cytosines (tC and tC O frameworks) have emerged as a unique class of fluorescent nucleobase analogues that minimally perturb the structure B‐form DNA are not quenched in duplex nucleic acids. Systematic derivatization these frameworks is likely approach to improve on diversify photophysical properties, but has so far been examined. Synthetic methods were refined tolerance for electron‐donating electron‐withdrawing groups, resulting series eight new, cytidine analogues....
The synthesis of a portion the challenging β1,2-mannosyl polymer found in cell walls Candida albicans was undertaken to develop conjugate vaccine against C. and facilitate NMR conformational studies this unique polysaccharide. novel approach tetrasaccharide 1 employed modified ulosyl bromide 11 as glycosyl donor which provided high diastereoselectivity. A participating solvent well p-chlorobenzyl protection facilitated new approach.
Fluorescent DNA of high molecular weight is an important tool for studying the physical properties and DNA-protein interactions, it plays a key role in modern biotechnology sequencing detection. While several polymerases can incorporate large numbers dye-linked nucleotides into primed templates, amplification resulting densely labeled strands by polymerase chain reaction (PCR) problematic. Here, we report method density labeling PCR reactions employing 5'-triphosphate...
Pyrogallol[4]arene hexamers are hydrogen-bonded molecular capsules of exceptional kinetic stability that can entrap small molecule guests indefinitely, without exchange, at ambient temperatures. Here, we report on the use a ball mill to induce self-assembly capsule components and in solid state. Stoichiometric amounts pyrogallol[4]arene guest, which be an arene, alkane, amine, or carboxylic acid, were milled 30 Hz for fixed durations, dissolved, characterization by NMR. Most resulting...
Human DNA primase synthesizes short RNA primers that polymerase alpha then elongates during the initiation of all new strands. Even though misincorporates NTPs at a relatively high frequency, this likely does not impact final product since primer is replaced with DNA. We used an extensive series purine and pyrimidine analogues to provide further insights into mechanism by which chooses whether or polymerize NTP. Primase readily polymerized size-expanded cytosine analogue,...
The use of capsules and cavitands in physical organic chemistry is briefly reviewed, their application to the study salt bridges introduced. Carboxylate/ammonium ion pairs are generated within an environment that more or less surrounds functional groups a synthetic fixed introverted solvent sphere. This provided by fold around amines present them with carboxylic acid function. Both water-soluble versions were prepared, equilibrium affinities quinuclidine bases determined NMR methods....
A resorcin[6]arene with an r-trans-cis-trans-cis-trans configuration of the pendant ethyl groups forms tubular crystal structures.
Zika virus (ZIKV), an emerging flavivirus that causes neurodevelopmental impairment to fetuses and has been linked Guillain-Barré syndrome continues threaten global health due the absence of targeted prophylaxis or treatment. Nucleoside analogues are good examples efficient anti-viral inhibitors, prodrug strategies using phosphate masking groups (ProTides) have employed improve bioavailability ribonucleoside analogues. Here, we synthesized tested a small library 13 ProTides against ZIKV in...