A fluorescent electrophile for CLIPS: self indicating TrkB binders.

Combination of cysteine-containing peptides with electrophiles provides efficient access to cyclo-organopeptides. However, there are no routes to intrinsically fluorescent cyclo-organopeptides containing robust, brilliant fluorophores emitting at wavelengths longer than cellular autofluorescence. We show such fluorescent cyclo-organopeptides can be made via SNAr reactions of cysteine-containing peptides with a BODIPY system. Seven compounds of this type were prepared to test as probes; six contained peptide sequences corresponding to loop regions in brain-derived neurotrophic factor and neurotrophic factor 4 (BDNF and NT-4) which bind tropomyocin receptor kinase B (TrkB). Cellular assays in serum-free media indicated two of the six key compounds induced survival of HEK293 cells stably transfected with TrkB whereas a control did not. The two compounds inducing cell survival bound TrkB on those cells (Kd ∼40 and 47 nM), illustrating how intrinsically fluorescent cyclo-organopeptides can be assayed for quantifiable binding to surface receptors in cell membrane environments.

Community-Based Recreational Therapy for Veterans with Behavioral Health Disorders: Impacts on Quality of Life, Participation, and Happiness.

Identifying evidenced-based interventions that improve health outcomes for Veterans with behavioral health disorders is a national priority. Thus, this study examined the outcomes of a community-based recreational therapy (RT) program focused on health promotion for Veterans with behavioral health disorders. Fifty-five Veterans with disabilities completed pretest and posttest questionnaires that assessed Quality of Life (QOL), Participation, and Happiness. Significant improvements were found in Overall QOL, Environmental QOL, Psychological QOL, QOL Rated, Satisfaction with Health, Participation, and Happiness. Younger age and female gender were significantly associated with improved Overall QOL. Factors significantly associated with improved Environmental QOL included younger age and non-Caucasian race. Older age was significantly associated with improved Participation. Female gender was positively associated with improved Happiness, while being divorced/separated was negatively associated with Happiness. These results have important implications for the use and expansion of community-based RT health promotion programs for Veterans with behavioral health disorders.

Productive Manipulation of Cyanine Dye π-Networks.

Polymethine bridges in cyanine dyes may be constrained by setting them into edge-fused ring systems, or extended by conjugation with carefully chosen heterocycles. Recent studies have shown that modifications like these can give significantly brighter dyes with red-shifted absorbance and emission maxima.

Hofmeister Anion Effects on Thermodynamics of Caffeine Partitioning between Aqueous and Cyclohexane Phases.

Specific anion effects on the thermodynamics of caffeine partitioning between aqueous and cyclohexane phases were studied in the presence of 11 sodium salts by utilizing UV-vis spectroscopy. It is observed that weakly hydrated anions such as ClO4-, SCN-, and I- salt caffeine into the aqueous phase and increase the standard Gibbs free energy for caffeine transfer. On the other hand, well-hydrated anions such as CO32- and SO42- salt caffeine molecules out of the aqueous solution and promote the transfer process. Results suggest that weakly hydrated anions associate with the hydrophobic patches of caffeine including three methyl groups and a flat heteroatomic ring to solvate caffeine molecules. Well-hydrated anions are excluded from the caffeine surface to salt caffeine molecules out of aqueous solution. Moreover, the enthalpy and entropy of caffeine transfer were obtained by measuring the standard Gibbs free energy for caffeine transfer at varied temperatures. The transfer of caffeine from the aqueous to cyclohexane phase was an endothermic process driven by the entropy of caffeine transfer. However, the trend in standard Gibbs free energy across the Hofmeister series was determined by the enthalpy of caffeine transfer. These results provide an enthalpic origin to explain the Hofmeister trends in aqueous solution.