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

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

NACA Research Memorandums

Report presenting an investigation to determine the effects of forging temperatures and solution treatments on the engine performance of Inconel 700 buckets. The buckets were tested in a J33-9 turbojet engine at 1625 degrees F in 20-minute cycles. Testing demonstrated that the buckets are capable of operating for more than 450 hours at rated speed

NACA Research Memorandums

Report presenting an investigation to study the origin and development of leading-edge cracking in turbine buckets made of six materials: S-816, M-252, Inconel 550, Inconel 700, Hastelloy R-235, and Jetalloy 1570. Some of the buckets were also given certain stress-relief treatments. Results regarding the development of leading-edge cracks, development of bucket fractures, comparison of performance for the material tested, macro- and microexamination of unfractured and fractured buckets

Glucose-Responsive Disassembly of Polymersomes of Sequence-Specific Boroxole-Containing Block Copolymers under Physiologically Relevant Conditions

Polymers containing organoboronic acids have recently gained interest as sugar-responsive materials owing to the reversible binding of saccharides to boronic acids, which triggers a change in the physical and chemical properties of these polymers, such as their water solubility. In particular, the ability of these polymers to bind glucose has attracted considerable attention because of the promise of these materials for the development of sensors and drug delivery systems for glucose-related human diseases, such as diabetes. We report here a new class of sugar-responsive polymers that are based on a sequence-specific copolymer of styreneboroxole and N-functionalized maleimide. The reversible addition-fragmentation and chain transfer (RAFT) polymerization of this pair of monomers ensured that a glucose receptor alternates with a nonresponsive solubilizing group throughout the sugar-responsive polymer chain. Due to the presence of hydrophilic solubilizing groups beween the solubility-switching boroxole moieties in the membrane-forming block, the polymersomes of the block copolymers responded to a lower level of glucose in the medium, resulting in diassembly of the bilayer membrane under a physiologically relevant pH and glucose level.clos