Allosteric inhibition of carnosinase (CN1) by inducing a conformational shift.

In humans, low serum carnosinase (CN1) activity protects patients with type 2 diabetes from diabetic nephropathy. We now characterized the interaction of thiol-containing compounds with CN1 cysteine residue at position 102, which is important for CN1 activity. Reduced glutathione (GSH), N-acetylcysteine and cysteine (3.2 ± 0.4, 2.0 ± 0.3, 1.6 ± 0.2 µmol/mg/h/mM; p < .05) lowered dose-dependently recombinant CN1 (rCN1) efficiency (5.2 ± 0.2 µmol/mg/h/mM) and normalized increased CN1 activity renal tissue samples of diabetic mice. Inhibition was allosteric. Substitution of rCN1 cysteine residues at position 102 (Mut1C102S) and 229 (Mut2C229S) revealed that only cysteine-102 is influenced by cysteinylation. Molecular dynamic simulation confirmed a conformational rearrangement of negatively charged residues surrounding the zinc ions causing a partial shift of the carnosine ammonium head and resulting in a less effective pose of the substrate within the catalytic cavity and decreased activity. Cysteine-compounds influence the dynamic behaviour of CN1 and therefore present a promising option for the treatment of diabetes.

The preferential deposition of micro-particles at the boundary of inkjet printed droplets.

The deposition behaviour of uniformly sized silica particles in drying aqueous droplets has been investigated for a range of particle sizes, 0.33, 1, 3 and 5 µm, in order to gain an improved understanding of the coffee drop effect. The droplets were produced by inkjet printing, which allowed multiple droplets of similar volume to be studied. Our observations show that particle size and the contact angle formed by the solvent droplet with the substrate determine how close to the boundary a particle is deposited. After drying, it was found that if the contact angle was less than 90°, smaller particles were located closer to the original droplet's periphery than larger particles in similar sized droplets. This deposition of particles can be explained by the wedge shape of the drying droplet's edge, which physically limits the movement of particles towards the droplet's periphery. In this paper we show that the size of a suspended particle influences the final dried morphology of a printed feature.

Inkjet printing of polyurethane colloidal suspensions.

An aqueous 40 wt% dispersion of polyurethane has been successfully printed at room temperature using a piezoelectric inkjet printer. Simple layered structures, as well as dots, were made and subsequently analyzed using white-light interferometry. A single layer was found to have a structure height of 10 µm; a value that suggests that this polyurethane dispersion may be suitable for use in rapid prototyping, since tall structures can be rapidly produced using only a few printing passes. Finally, by the simple addition of a water-soluble dye, colour gradients were produced using this printing technique.

Automated multiple-layer spotting for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of synthetic polymers utilizing ink-jet printing technology.

Recently, a new multiple-layer matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) sample spotting technique for poly(ethylene glycol), offering improved analysis possibilities, was described. In this contribution the application of ink-jet printing to automated, multiple-layer MALDI-TOFMS sample preparation of synthetic polymers is presented, allowing accurate deposition of matrix, additive and analyte solutions. The new sample preparation technique was evaluated for poly(ethylene glycol) as well as poly(methyl methacrylate) standards, and optimized settings for both synthetic polymers have been obtained.