Discovery of a Novel Activator of KCNQ1-KCNE1 K+ Channel Complexes

KCNQ1 voltage-gated K+ channels (Kv7.1) associate with the family of five KCNE peptides to form complexes with diverse gating properties and pharmacological sensitivities. The varied gating properties of the different KCNQ1-KCNE complexes enables the same K+ channel to function in both excitable and non excitable tissues. Small molecule activators would be valuable tools for dissecting the gating mechanisms of KCNQ1-KCNE complexes; however, there are very few known activators of KCNQ1 channels and most are ineffective on the physiologically relevant KCNQ1-KCNE complexes. Here we show that a simple boronic acid, phenylboronic acid (PBA), activates KCNQ1/KCNE1 complexes co-expressed in Xenopus oocytes at millimolar concentrations. PBA shifts the voltage sensitivity of KCNQ1 channel complexes to favor the open state at negative potentials. Analysis of different-sized charge carriers revealed that PBA also targets the permeation pathway of KCNQ1 channels. Activation by the boronic acid moiety has some specificity for the Kv7 family members (KCNQ1, KCNQ2/3, and KCNQ4) since PBA does not activate Shaker or hERG channels. Furthermore, the commercial availability of numerous PBA derivatives provides a large class of compounds to investigate the gating mechanisms of KCNQ1-KCNE complexes

Non Inflammatory Boronate Based Glucose-Responsive Insulin Delivery Systems

Boronic acids, known to bind diols, were screened to identify non-inflammatory cross-linkers for the preparation of glucose sensitive and insulin releasing agglomerates of liposomes (Agglomerated Vesicle Technology-AVT). This was done in order to select a suitable replacement for the previously used cross-linker, ConcanavalinA (ConA), a lectin known to have both toxic and inflammatory effects in vivo. Lead-compounds were selected from screens that involved testing for inflammatory potential, cytotoxicity and glucose-binding. These were then conjugated to insulin-encapsulating nanoparticles and agglomerated via sugar-boronate ester linkages to form AVTs. In vitro, the particles demonstrated triggered release of insulin upon exposure to physiologically relevant concentrations of glucose (10 mmoles/L–40 mmoles/L). The agglomerates were also shown to be responsive to multiple spikes in glucose levels over several hours, releasing insulin at a rate defined by the concentration of the glucose trigger

Influence of particle size on appearance and in vitro efficacy of sunscreens

Nanotechnology applies to diverse sectors of science. In cosmetic area, investments have strengthened the idea that nanoproducts provide innumerable benefits to consumers. Extreme exposition to solar light can cause undesirable effects, thus, adding UV filters in cosmetic products are often used as prevention. Ethylhexyl methoxycinnamate and benzophenone-3 are UV filters widely used in sunscreen formulations, this UV filters absorb UVB and UVA radiation, respectively. In this study, sunscreen formulations were developed as nano and macroemulsion, but composed by the same raw material. Nanoemulsion was obtained by phase inversion temperature method (PIT). Physical and functional properties were evaluated by visual analysis, particle size distribution and by diffuse reflectance spectrophotometry. Achieved nanoemulsion showed bluish brightness aspect, less apparent consistency than macroemulsion, stability longer than 48 hours (22.0 ± 2.0 °C) and bimodal particle size distribution with average (mean) sizes around 10 nm (61%) and 4.5 µm (39%). Macroemulsion showed milky aspect, higher consistency than nanoemulsion, instability after 48 hours (22.0 ± 2.0 °C) and bimodal particle size distribution with average (mean) size around 202 nm (9%) and 10.4 µm (91%). Effectiveness profile of sunscreen formulations remained apparently similar, based on achieved results of in vitro SPF, UVA/UVB ratio and critical wavelength assays

Gelatin-based microspheres crosslinked with glutaraldehyde and rutin oriented to cosmetics

ABSTRACT Glutaraldehyde (GTA) has been extensively used as a gelatin crosslinking agent, however, new natural ones have been suggested as more biocompatible. Polyphenols are possible candidates and the flavonols, such as rutin (RUT), also exhibit potential synergism with sunscreens and antioxidant agents used in cosmetics. In this work, gelatin microspheres (M0) were obtained and crosslinked with GTA 10 mM (MG) or RUT 10 mM (MR), dissolved in acetone:NaOH 0,01M (70:30 v/v). MG exhibited crosslinking extent of 54.4%. Gelatin, M0, MG and MR did not elicit any signs of skin damage, regarding the formation of erythema, the barrier function disruption and negative interference in the stratum corneum hydration. Oily dispersions containing M0, MG or MR, isolated or combined with benzophenone-3 or octyl methoxycinnamate, suggested that the microspheres, at a 5.0% w/w, had no additional chemical or physical photoprotective effect in vitro. Crosslinking with RUT had occurred, but in a lower degree than GTA. Microspheres had not improved sun protection parameters, although, non-treated gelatin interfered positively with the SPF for both UV filters. The in vivo studies demonstrated that these materials had very good skin compatibility

The mechanisms of boronate ester formation and fluorescent turn-on in ortho-aminomethylphenylboronic acids

ortho-Aminomethylphenylboronic acids are used in receptors for carbohydrates and various other compounds containing vicinal diols. The presence of the o-aminomethyl group enhances the affinity towards diols at neutral pH, and the manner in which this group plays this role has been a topic of debate. Further, the aminomethyl group is believed to be involved in the turn-on of the emission properties of appended fluorophores upon diol binding. In this treatise, a uniform picture emerges for the role of this group: it primarily acts as an electron-withdrawing group that lowers the pK(a) of the neighbouring boronic acid thereby facilitating diol binding at neutral pH. The amine appears to play no role in the modulation of the fluorescence of appended fluorophores in the protic-solvent-inserted form of the boronic acid/boronate ester. Instead, fluorescence turn-on can be consistently tied to vibrational-coupled excited-state relaxation (a loose-bolt effect). Overall, this Review unifies and discusses the existing data as of 2019 whilst also highlighting why o-aminomethyl groups are so widely used, and the role they play in carbohydrate sensing using phenylboronic acids

Boronic acids for sensing and other applications - a mini-review of papers published in 2013

Boronic acids are increasingly utilised in diverse areas of research. Including the interactions of boronic acids with diols and strong Lewis bases as fluoride or cyanide anions, which leads to their utility in various sensing applications. The sensing applications can be homogeneous assays or heterogeneous detection. Detection can be at the interface of the sensing material or within the bulk sample. Furthermore, the key interaction of boronic acids with diols allows utilisation in various areas ranging from biological labelling, protein manipulation and modification, separation and the development of therapeutics. All the above uses and applications are covered by this mini-review of papers published during 2013