Proximity Ligation‐Based Fluorogenic Imaging Agents for Neuraminidases

Reagents to visualize and localize neuraminidase activity would be valuable probes to study the role of neuraminidases in normal cellular processes as well as during viral infections or cancer development. Herein, a new class of neuraminidase‐imaging probes that function as proximity ligation reagents by releasing a highly reactive fluorophore that tags nearby cellular material is described. It is further demonstrated that it is possible to create an influenza virus‐specific reagent, which can specifically detect influenza virus infections in mammalian cells. These reagents have potential use as specific histological probes independent of viral antigenicity and, therefore, offer some advantages over commonly used anti‐neuraminidase antibodies.     

Polymerizable derivatives of long-chain fatty acids. IV. Vinyl esters

Contrary to some published reports, the vinyl esters of saturated fatty acids polymerize readily and rapidly. Vinyl oleate, when present in excess of 5%, and oxygen exert marked retarding effects. Techniques are described for the free-radical-initiated polymerization of the vinyl esters of caprylic, capric, lauric, myristic, palmitic, and stearic acids in bulk, dispersion, solution, and emulsion. Some data are given for polymerization in the presence of chain-transfer agents, such as carbon tetrachloride, dodecylmercaptan, and ethylbenzene. Conditions are reported for obtaining degrees of polymerization from about 2 (when chain-transfer agents are employed) to 10,000 (weight average). The weight average degree of polymerization increases markedly as the conversion increases, particularly above 80%. Even up to extremely high conversions, soluble polymers are obtained in most cases. Solubility characteristics, transition point data, molecular weights (osmometric and light-scattering), and isolation and purification techniques are also reported.     

Expansions for Log Densities of Multivariate Estimates

Withers and Nadarajah (Stat Pap 51:247–257; 2010) gave simple Edgeworth-type expansions for log densities of univariate estimates whose cumulants satisfy standard expansions. Here, we extend the Edgeworth-type expansions for multivariate estimates with coefficients expressed in terms of Bell polynomials. Their advantage over the usual Edgeworth expansion for the density is that the kth term is a polynomial of degree only k + 2, not 3k. Their advantage over those in Takemura and Takeuchi [Sankhyā, A, 50, 1998, 111-136] is computational efficiency     

Alternative donor substrates for inverting and retaining glycosyltransferases

By the use of glycosyl donors containing aromatic leaving groups linked with opposite anomeric configurations compared to those of the natural donor substrates, an inverting (Cst II) and a retaining (LgtC) glycosyltransferase were found to catalyse glycosylation reactions of natural acceptor substrates in the presence of the corresponding nucleotide.     

Lipid-mimicking phosphorus-based glycosidase inactivators as pharmacological chaperones for the treatment of Gaucher's disease

Gaucher''s disease, the most prevalent lysosomal storage disorder, is caused by missense mutation of the GBA gene, ultimately resulting in deficient GCase activity, hence the excessive build-up of cellular glucosylceramide. Among different therapeutic strategies, pharmacological chaperoning of mutant GCase represents an attractive approach that relies on small organic molecules acting as protein stabilizers. Herein, we expand upon a new class of transient GCase inactivators based on a reactive 2-deoxy-2-fluoro-β-d-glucoside tethered to an array of lipid-mimicking phosphorus-based aglycones, which not only improve the selectivity and inactivation efficiency, but also the stability of these compounds in aqueous media. This hypothesis was further validated with kinetic and cellular studies confirming restoration of catalytic activity in Gaucher cells after treatment with these pharmacological chaperones.

Engineered 2-fluoroglucosides containing a phosphorus-based leaving group rapidly form a stable covalent intermediate with GCase, thus stabilising the enzyme during transit to the lysosome, where it is released on a clinically appropriate timescale.     

A Chemoenzymatic Total Synthesis of the Neurogenic Starfish Ganglioside LLG-3 Using an Engineered and Evolved Synthase

An LLG-3 oligosaccharide-fluoride can be assembled chemoenzymatically and readily coupled with various sphingosines by an engineered endoglycoceramidase glycosynthase. The lyso?ganglioside products are acylated to generate the individual isomers identified in the heterogeneous natural isolates, as well as modified glycosphingolipids.     

Melting Point and Composition Distribution of Polyolefins by Fractionation

The fractionation technique described in this paper was used to characterize the melting-point, monomer, and blocking distributions for polymers and copolymers. It is different from the molecular-weight fractionation technique in that the fractions are obtained by using a single solvent to extract the solid polymer below its melting point at stepwise-increasing temperatures. The reproducibility of this technique is excellent, and the technique is sufficient to distinguish pellet-to-pellet variation in a commercially available polypropylene. It was used to show the influence of preparation variables on the melting-point distributions of polyethylene and polypropylene and on the monomer and blocking distribution of copolymers, and to distinguish copolymers from blends.