Publications by authors named "Ryan T Lee"

The installation of fluorine and fluorinated functional groups in organic molecules perturbs the physicochemical properties of those molecules and enables the development of new therapeutics, agrichemicals, biological probes and materials. However, current synthetic methodologies cannot access some fluorinated functional groups and fluorinated scaffolds. One such group, the -difluorobenzyl motif, might be convergently synthesized by reacting a nucleophilic aryl precursor and an electrophilic -difluoroalkene.

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Nonionic surfactant excipients (NISEs) are commonly added to biologics formulations to mitigate the effects of stress incurred by the active biotherapeutic during manufacturing, transport, and storage. During manufacturing, NISEs are added by dilution of a stock solution directly into a protein formulation, and their accurate addition is critical in maintaining the quality and integrity of the drug product and thus ensuring patient safety. This is especially true for the common NISEs, polysorbates 20 and 80 (PS20 and PS80, respectively) and poloxamer 188 (P188).

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The installation of fluorine and fluorinated functional groups into drug-like scaffolds can perturb the physicochemical, pharmacokinetic, and pharmacodynamic properties of compounds. However, some potentially useful fluorinated substructures reside predominantly outside the realm of the current synthetic methodologies. One such substructure, the α,α-difluorophosphine oxide, might be convergently prepared by the reaction of a -difluorinated alkene with a P-H bond, though such nucleophilic reactions instead proceed through a C-F substitution pathway that delivers monofluorovinyl products.

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In this project, we have studied the use of electrical impedance cardiography as a possible method for measuring blood pulse wave velocity, and hence be an aid in the assessment of the degree of arteriosclerosis. Using two different four-electrode setups, we measured the timing of the systolic pulse at two locations, the upper arm and the thorax, and found that the pulse wave velocity was in general higher in older volunteers and furthermore that it was also more heart rate dependent for older subjects. We attribute this to the fact that the degree of arteriosclerosis typically increases with age and that stiffening of the arterial wall will make the arteries less able to comply with increased heart rate (and corresponding blood pressure), without leading to increased pulse wave velocity.

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Tunable erosion of polymeric materials is an important aspect of tissue engineering for reasons that include cell infiltration, controlled release of therapeutic agents, and ultimately to tissue healing. In general, the biological response to proteinaceous polymeric hydrogels is favorable (e.g.

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A membrane alignment technique has been used to measure the distance between two TOAC nitroxide spin labels on the membrane-spanning M2δ, peptide of the nicotinic acetylcholine receptor (AChR), via CW-EPR spectroscopy. The TOAC-labeled M2δ peptides were mechanically aligned using DMPC lipids on a planar quartz support, and CW-EPR spectra were recorded at specific orientations. Global analysis in combination with rigorous spectral simulation was used to simultaneously analyze data from two different sample orientations for both single- and double-labeled peptides.

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Wild-type phospholamban (WT-PLB), a Ca(2+)-ATPase (SERCA) regulator in the sarcoplasmic reticulum membrane, was studied using TOAC nitroxide spin labeling, magnetically aligned bicelles, and electron paramagnetic resonance (EPR) spectroscopy to ascertain structural and dynamic information. Different structural domains of PLB (transmembrane segment: positions 42 and 45, loop region: position 20, and cytoplasmic domain: position 10) were probed with rigid TOAC spin labels to extract the transmembrane helical tilt and structural dynamic information, which is crucial for understanding the regulatory function of PLB in modulating Ca(2+)-ATPase activity. Aligned experiments indicate that the transmembrane domain of wild-type PLB has a helical tilt of 13°±4° in DMPC/DHPC bicelles.

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