Toward bioinspired galectin mimetics: identification of ligand-contacting peptides by proteolytic-excision mass spectrometry

Clinically relevant bioactivities of human galectins (adhesion/growth-regulatory galactoside-specific lectins) inspired the design of peptides as new tools to elicit favorable effects (e.g., in growth control) or block harmful binding (e.g., in tissue invasion). To obtain the bioinspired lead compounds, we combined a proteolytic fragmentation approach without/with ligand contact (excision) with mass spectrometric identification of affinity-bound protein fragments, using galectin-1 and -3 as models. Two peptides from the carbohydrate recognition domains were obtained in each case in experimental series rigorously controlled for specificity, and the [157-162] peptide of galectin-3 proved to be active in blocking lectin binding to a neoglycoprotein and to tumor cell surfaces. This approach affords peptide sequences for structural optimization and intrafamily/phylogenetic galectin comparison at the binding-site level with a minimal requirement of protein quantity, and it is even amenable to mixtures.     

Regiochemistry in cobalt-mediated intermolecular Pauson-Khand reactions of unsymmetrical internal heteroaromatic alkynes with norbornene

The intermolecular Pauson-Khand (PK) reactions of sterically comparable (2-phenylethynyl)heteroaromatic compounds with norbornene, mediated by Co(2)(CO)(8) to give cyclopentenone products, were examined in this study. A synthetic protocol utilizing focused-microwave dielectric heating proved indispensable in the efficient synthesis of the PK cyclopentenone products. "π-Deficient" heteroaromatic substrates, e.g., 2-pyrones, and some "π-excessive" heteroaromatics such as 2- and 3-thiophene and 2-furan favor the β-position in the newly formed cyclopentenone ring. Other π-excessive heteroaromatics such as 2-pyrrole or 2-indole favor the α-position. A π-excessive 3-indole derivative gave a nearly equal mixture of regioisomers. The position of the nitrogen in pyridyl-containing alkyne substrates also affects the regiochemical outcome of the PK reaction. A 2-pyridyl alkyne, possessing a proximal nitrogen, influences the regioselectivity relative to a 4-pyridyl variant quite dramatically, favoring the β-position in the newly formed cyclopentenone ring. A 2-pyrimidylalkyne exhibits similar behavior to the 2-pyridylalkyne. Compounds that do not participate in PK reactions with norbornene include (2-phenylethynyl)imidazoles and the related benzimidazoles, which promote rapid decomposition of the in situ generated (μ(2)-alkyne)Co(2)(CO)(6) complexes. This stands in contrast with other nitrogen-containing heteroaromatics, e.g., pyrrole-, indole-, and pyrimidine-derived compounds, which effectively undergo PK reactions. Overall, the type of heteroaromatic group dramatically influences PK regioselectivity, which can in part be explained by rationalization of the current reaction mechanism, but not fully.     

Synthesis, characterization, and spectroscopic characteristics of chromium(6+) and -(4+) silicalite-2 (ZSM-11) materials

The systematic incorporation of Cr ions into a phase-pure silicalite-2 lattice was accomplished through hydrothermal synthesis using 3,5-dimethylpiperidinium as a templating agent. The Cr ions, after calcination to remove the template, were in the 6+ oxidation state, with their incorporation into the lattice verified by the systematic expansion of the unit cell as a function of Cr loading. The structures of these materials as revealed by electronic spectroscopy and X-ray absorption near-edge spectroscopy (XANES) were consistent with the dioxo structure typically exhibited by Cr(6+) in an amorphous silica matrix. These materials were highly luminescent, with the emission spectra showing an unusually well-resolved vibronic structure characteristic of an emissive site with little inhomogeneous broadening. The site was reduced under flowing CO to Cr(4+), as characterized by XANES. The reduction of Cr from 6+ to 4+ resulted in unit-cell volumes that are systematically smaller than those observed with Cr(6+), even though the ionic radius of Cr(4+) is larger. This is attributed to the fact that the Cr(6+) site is not a simple metal ion but a significantly larger [CrO(2)](2+) unit, requiring a larger lattice expansion to accommodate it. Through analysis of the XANES preedge and assignment of the ligand-field spectrum of the Cr(4+) ions, it is possible to establish isomorphic substitution into the silicalite lattice.     

Preparative separation of 1,3,6-pyrenetrisulfonic acid trisodium salt from the color additive D&C Green No. 8 (pyranine) by pH-zone-refining counter-current chromatography

In developing analytical methods for batch certification of the color additive D&C Green No. 8 (G8), the U.S. Food and Drug Administration needed the trisodium salt of 1,3,6-pyrenetrisulfonic acid (P3S) for use as a reference material. Since P3S was not commercially available, preparative quantities of it were separated from portions of a sample of G8 that contained ～3.5% P3S. The separations were performed by pH-zone-refining counter-current chromatography using dodecylamine (DA) as the hydrophobic counterion. The added DA enabled partitioning of the polysulfonated components into the organic stationary phase of the two-phase solvent system used, 1-butanol-water (1:1). Thus, a typical separation that involved 20.3g of G8, using sulfuric acid as the retainer acid and 20% DA in the stationary phase and 0.1M sodium hydroxide as the mobile phase, resulted in ～0.58 g of P3S of greater than 99% purity. The identification and characterization of the separated P3S were performed by elemental analyses, proton nuclear magnetic resonance, high-resolution mass spectrometry, ultra-violet spectra, and high-performance liquid chromatography.     

Electrochemical investigation of a glassy carbon electrode modified with carbon nanotubes decorated with (poly)crystalline gold

Multiwalled carbon nanotubes with nanosized sputtered gold were used to modify a glassy carbon electrode (GCE). The substrate was characterized by scanning electron microscopy (SEM), X-ray diffraction, cyclic voltammetry and amperometry. SEM micrographs indicated an uniform coverage of the carbon nanotubes with nanosized (poly)crystalline gold. Cyclic voltammetry reveals that peak separation of the unmodified GCE in the presence of 1?mM ferricyanide is 131?mV, but 60?mV only for the modified GCE. In addition, the oxidation of NADH (1?mmol?L^?1 solution) begins at negative potentials (around ?100?mV vs. Ag/AgCl), and the anodic peak potential (corresponding to the irreversible oxidation of NADH) is found at +94?mV. The effect of pH on the electrocatalytic activity was studied in the range from 5.4 to 8.0. The relationship between the anodic peak potential and the pH indicated a variation of ?33.5?mV/pH which is in agreement with a two-electron and one-proton reaction mechanism. Amperometry, performed at either ?50 or +50?mV vs. an Ag/AgCl reference electrode, indicates that the modified electrode is a viable amperometric sensor for NADH. At a working potential of +50?mV, the response to NADH is linear in the concentration range from 1 to 100???mol?L^?1, with an RSD of 6% (n?=?4).

Thermodynamic parameters and counterion binding to the micelle in binary anionic surfactant systems

Competitive counterion binding of sodium and calcium to micelles, and mixed micellization have been investigated in the systems sodium dodecylsulfate (NaDS)/sodium decylsulfate (NaDeS) and NaDS/sodium 4-octylbenzenesulfonate (NaOBS) in order to accurately model the activity of the relevant species in solution. The critical micelle concentration (CMC) and equilibrium micelle compositions of mixtures of these anionic surfactants, which is necessary for determining fractional counterion binding measurements, is thermodynamically modeled by regular solution theory. The mixed micelle is ideal (the regular solution parameter β(M)=0) for the NaDS/NaOBS system, while the mixed micelle for NaDS/NaDeS has β(M)=-1.05 indicating a slight synergistic interaction. Counterion binding of sodium to the micelle is influenced by the calcium ion concentration, and vice versa. However, the total degree of counterion binding is essentially constant at approximately 0.65 charge negation at the micelle's surface. The counterion binding coefficients can be quantitatively modeled using a simple equilibrium model relating concentrations of bound and unbound counterions.     

New bounds on the average distance from the Fermat–Weber center of a planar convex body

The Fermat–Weber center of a planar body Q is a point in the plane from which the average distance to the points in Q is minimal. We first show that for any convex body Q in the plane, the average distance from the Fermat–Weber center of Q to the points in Q is larger than , where Δ(Q) is the diameter of Q. This proves a conjecture of Carmi, Har-Peled and Katz. From the other direction, we prove that the same average distance is at most . The new bound substantially improves the previous bound of due to Abu-Affash and Katz, and brings us closer to the conjectured value of . We also confirm the upper bound conjecture for centrally symmetric planar convex bodies.     

Corrector-predictor methods for sufficient linear complementarity problems

We present a new corrector-predictor method for solving sufficient linear complementarity problems for which a sufficiently centered feasible starting point is available. In contrast with its predictor-corrector counterpart proposed by Miao, the method does not depend on the handicap κ of the problem. The method has \(O((1+\kappa)\sqrt{n}L)\)-iteration complexity, the same as Miao’s method, but our error estimates are sightly better. The algorithm is quadratically convergent for problems having a strictly complementary solution. We also present a family of infeasible higher order corrector-predictor methods that are superlinearly convergent even in the absence of strict complementarity. The algorithms of this class are globally convergent for general positive starting points. They have \(O((1+\kappa)\sqrt{n}L)\)-iteration complexity for feasible, or “almost feasible”, starting points and O((1+κ)² nL)-iteration complexity for “sufficiently large” infeasible starting points.     

Numerical calculation of the neutral fermion gap at the ν=5/2 fractional quantum Hall state

We present the first numerical computation of the neutral fermion gap, Δ(F), in the ν=5/2 quantum Hall state, which is analogous to the energy gap for a Bogoliubov-de Gennes quasiparticle in a superconductor. We find Δ(F)≈0.027e(2)/ε?(0), comparable to the charge gap. We also deduce an effective Fermi velocity v(F) for neutral fermions from the low-energy spectra for odd numbers of electrons, and thereby obtain a correlation length ξ(F)=v(F)/Δ(F)≈1.3?(0). We comment on implications for experiments, topological quantum information processing, and electronic mechanisms of superconductivity.     

Neutron powder diffraction and magnetic studies of mesoporous Co3O4

Samples of mesoporous Co₃O₄, created by using mesoporous silicas KIT-6 and SBA-16 as hard templates to control the growth of Co₃O₄ have been investigated with SQUID magnetometry and neutron powder diffraction, to reveal the effects of high surface area on the magnetic and electronic properties. DC magnetic susceptibility measurements show lower Néel ordering temperatures and lower magnetic moments than in a “bulk” reference. A lower second transition temperature is also observed in the mesoporous samples, associated with the freezing of the surface (shell) magnetic moments. Measurements taken with increasing applied field at constant temperature show the materials to be antiferromagnetic as expected. Complementary parametric neutron powder diffraction studies show similar trends between the two mesoporous samples when looking at their Néel temperatures, and verify long range order within the samples.