@article {https://doi.org/10.1002/elps.202300245, title = {Numerical modeling and experimental optimization of Taylor dispersion analysis with and without an electric field}, journal = {ELECTROPHORESIS}, volume = {45}, number = {n/a}, year = {2024}, pages = {in press}, abstract = {

Abstract Numerical modeling of Taylor dispersion analysis (TDA) was performed using COMSOL Multiphysics to facilitate better and faster optimization of the experimental conditions. Parameters, such as pressure, electric field, diameter, and length of capillary on the TDA conditions, were examined for particles with hydrodynamic radius (Rh) of 2.5\–250\ {\r A}. The simulations were conducted using 25, 50, and 100\ cm length tubes with diameters of 25, 50, and 100\ \µm. It was shown that particles with larger diffusion coefficients gave more accurate results at higher velocities, and in longer and wider columns; particles with smaller diffusion coefficients gave more accurate results at smaller velocities, and in shorter and thinner columns. Moreover, the effect of electric field on the validity and the applicability of TDA was studied using TDA in conjunction with capillary electrophoresis. Diffusion coefficients were obtained using a pressure and the TDA equation and compared with those obtained with a pressure in combination of an electric field for fluorescein, FD4, FD20, FD70, and FD500. We found that TDA can be used with the presence of moderate electrophoretic migration and electroosmotic flow, when appropriate conditions were met.

}, keywords = {capillary electrophoresis, DIFFUSION, hydrodynamic radius, numerical modeling, Taylor dispersion analysis}, doi = {https://doi.org/10.1002/elps.202300245}, url = {https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elps.202300245}, author = {Chenyakin, Yuri and Chen, David D. Y.} } @article {https://doi.org/10.1002/elps.202200279, title = {β-Cyclodextrin and folic acid host{\textendash}guest interaction binding parameters determined by Taylor dispersion analysis and affinity capillary electrophoresis}, journal = {ELECTROPHORESIS}, volume = {44}, number = {n/a}, year = {2023}, month = {03/2023}, type = {Research}, chapter = {in press}, abstract = {

Abstract The thermodynamic properties of molecular recognition in host\–guest inclusion complexes can be studied by Taylor dispersion analysis (TDA). Host\–guest inclusion complexes have modest size, and it is possible to get convergent results fast, achieving greater certainty for the obtained thermodynamic properties. Cyclodextrins (CDs) and their derivatives can be used as drug carriers that can boost stability, solubility, and bioavailability of physiologically active substances. A simple and effective approach for assessing the binding properties of CD complexes that are critical in the early stages of drug and formulation development is needed to fully understand the process of CD and guest molecules\’ complex formation. In this work, TDA was successfully used to rapidly determine interaction parameters, including binding constant and stoichiometry, between β-CD and folic acid (FA) along with the diffusivities of the free FA and its complex with β-CD. Additionally, the FA diffusion coefficient obtained by TDA was compared to the results previously obtained by nuclear magnetic resonance. Affinity capillary electrophoresis (ACE) was also used to compare the binding constants obtained by different methods. The results showed that the binding constants obtained by ACE were somewhat lower than those obtained by the two TDA procedures.

}, keywords = {affinity capillary electrophoresis, binding constant, cyclodextrin, folic acid, Taylor dispersion analysis}, doi = {https://doi.org/10.1002/elps.202200279}, url = {https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elps.202200279}, author = {Dai, Yuanli and Sun, Chang and Yang, Yunhe and Wang, Shuanghao and Li, Huihui and Chen, David D. Y.} } @article {YANG2021122533, title = {Detecting the formation of human c-KIT oncogene promoter G-Quadruplex by Taylor dispersion analysis}, journal = {Talanta}, volume = {233}, year = {2021}, pages = {122533}, abstract = {The formation of G-quadruplex (G4) structures in oncogenic G-rich promoter regions are implicated in their biological functions, especially the inhibition of transcription. The binding of cations is thought to contribute to the stabilization of the G4 formation and competition against the duplex formation in the genomic sequence. Furthermore, it might affect the recognition of DNA-binding proteins. Therefore, measuring the interaction between G4 DNA and cations in a free solution environment is critical for evaluating G4 DNA biological functions. However, how binding to cations (K+ and NH4+) affects the folding equilibrium of the G4 structure remains unclear. In this work, a Taylor dispersion analysis (TDA) method using a capillary electrophoresis (CE) instrument was established for the quantitative characterization of the cation-dependent G4 formation in the human c-KIT oncogene promoter region, as well as diffusivities and hydrodynamic radii of DNA variations before and after folding. Our results showed that both K+ and NH4+ can induce the random-coiled c-KIT DNA to unfold and form a more unstretched intermediate state and then fold into tightly structured G4s with smaller size. The G4 size induced by NH4+ was smaller than that induced by K+ ions, though these two cations induced the c-KIT G4 DNA formation with similar binding constants (order of magnitude around 106~M-1). The TDA method can be widely used for rapid structural analyses of trace amounts of DNA mixtures, which effectively differentiate DNA variations or DNA-ligand complex conformations.}, keywords = {binding constant, c-KIT oncogene, capillary electrophoresis, G-quadruplex, Taylor dispersion analysis}, issn = {0039-9140}, doi = {https://doi.org/10.1016/j.talanta.2021.122533}, url = {https://www.sciencedirect.com/science/article/pii/S0039914021004549}, author = {Yunhe Yang and Yang Yang and Shuangshuang Wang and Huihui Li and David D.Y. Chen} } @article {https://doi.org/10.1002/elps.202100077, title = {Quantitative characterization of human oncogene promoter G-quadruplex DNA-ligand interactions using a combination of mass spectrometry and capillary electrophoresis}, journal = {ELECTROPHORESIS}, volume = {42}, number = {n/a}, year = {2021}, month = {05/2021}, pages = {1450-1460}, type = {Research}, chapter = {1450}, abstract = {

Abstract Human c-KIT oncogene is known to regulate cell growth and proliferation, and thus, acts as a probable target in the treatment of gastrointestinal tumors (GIST). To identify small molecule ligands which can specifically bind with the G-quadruplex (G4) in the c-KIT promoter region as potential antitumor agents, we propose the combination of electrospray ionization\–mass spectrometry (ESI-MS), capillary electrophoresis frontal analysis (CE-FA), and Taylor dispersion analysis (TDA) to accurately investigate the G4/ligands binding properties. First, ESI\–MS was used for initial screening of natural products (NPs). CE-FA was then used to calculate specific binding constants and the stoichiometry of the native state binding pair in solution. Next, TDA, a micro-capillary flow technique was used to examine the effect of the ligand binding on the diffusivity and particle size of the c-KIT G4. Two of the screened NPs, scopolamine butylbromide (L1) and isorhamnetin-3-O-neohesperidoside (L3), were found to specifically bind to the c-KIT G4 with binding constants of around 104 M\–1 and 1:1 stoichiometry in a free solution. TDA data showed that ligand binding (both L1 and L3) induced the c-KIT strands to fold into a tightly structured G4 with a decreased hydrodynamic radius. These ligands have the potential to be drug candidates for the regulation of c-KIT gene transcription by stabilizing the G4 structure. This methodology not only increased the speed of analysis but also improved its accuracy and specificity compared with the conventional binding approaches.

}, keywords = {binding constant, c-KIT oncogene, Capillary electrophoresis frontal analysis, Electrospray ionization{\textendash}mass spectrometry, G-quadruplex, Taylor dispersion analysis}, doi = {https://doi.org/10.1002/elps.202100077}, url = {https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/elps.202100077}, author = {Wang, Shuangshuang and Yang, Yang and Yang, Yunhe and Li, Huihui and Chen, David D.Y.} }