An expedient synthesis of orthogonally protected lysinoalanine from Aloc-protected Garner’s aldehyde

An expedient synthesis of orthogonally protected lysinoalanine has been developed. We have prepared a novel Garner’s aldehyde derivative bearing an Aloc group; reductive amination of this aldehyde with Fmoc-Lys-OPMB gave the lysinoalanine skeleton. This was then transformed into an orthogonally protected lysinoalanine derivative suitable for the synthesis of side-chain bridged cyclic peptides by solid phase peptide synthesis methods.     

Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK,a metabolically resistant bradykinin B1 agonist,in a rat C6 glioma model

Background

While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model.

Results

SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area.

Conclusions

Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study.

     

Nilpotent pseudogroups of functions on an interval

A near-identity nilpotent pseudogroup of order m 1 is a family f ₁, . . . , f _n : (-1, 1) of C ² functions for which: for some small positive real number < 1/10 ^m+1 and commutators of the functions f _i of order at least m equal the identity. We present a classification of near-identity nilpotent pseudogroups: our results are similar to those of Plante, Thurston, Farb and Franks. As an application, we classify certain foliations of nilpotent manifolds.     

On the differentiability of first integrals of two dimensional flows

By using techniques of differential geometry we answer the following open problem proposed by Chavarriga, Giacomini, Giné, and Llibre in 1999. For a given two dimensional flow, what is the maximal order of differentiability of a first integral on a canonical region in function of the order of differentiability of the flow? Moreover, we prove that for every planar polynomial differential system there exist finitely many invariant curves and singular points , such that has finitely many connected open components, and that on each of these connected sets the system has an analytic first integral. For a homogeneous polynomial differential system in , there exist finitely many invariant straight lines and invariant conical surfaces such that their complement in is the union of finitely many open connected components, and that on each of these connected open components the system has an analytic first integral.     

Oxime functionalization strategy for iodinated poly(epsilon‐caprolactone) X‐ray opaque materials

Since two of the most common technologies for imaging the human body are X‐ray radiography and computed tomography (CT), researchers are focused on developing biodegradable and biocompatible polymeric molecules as an alternative to the traditional small molecule contrast agents. This report highlights the synthesis of novel biodegradable iodinated poly(ε‐caprolactone) copolymers by oxime “Click” ligation reactions. A series of ketone‐bearing materials are built by tin (II)‐mediated ring‐opening polymerization followed by a postpolymerization deprotection step. The intended X‐ray opacity is imparted through acid‐catalyzed oxime postpolymerization modification of the resultant polymers with an iodinated hydroxylamine. All small molecules and polymeric materials are characterized using proton nuclear magnetic resonance (NMR) for purity, functional group stoichiometry, and number‐averaged molecular weight calculations. Additionally, the polymers are evaluated with gel permeation chromatography (GPC) to determine polymer sample polydispersity and general molecular weight distribution shapes and by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) for thermal properties. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2421–2430     

Fluorescence biosensing micropatterned surfaces based on immobilized human acetylcholinesterase

Human acetylcholinesterase (AChE) is a widely studied target enzyme in drug discovery for Alzheimer’s disease (AD). In this paper we report evaluation of the optimum structure and chemistry of the supporting material for a new AChE-based fluorescence sensing surface. To achieve this objective, multilayered silicon wafers with spatially controlled geometry and chemical diversity were fabricated. Specifically, silicon wafers with silicon oxide patterns (SiO₂/Si wafers), platinum-coated silicon wafers with SiO₂ patterns (SiO₂/Pt/Ti/Si wafers), and Pt-coated wafers coated with different thicknesses of TiO₂ and SiO₂ (SiO₂/TiO₂/Pt/Ti/Si wafers) were labelled with the fluorescent conjugation agent HiLyte Fluor 555. Selection of a suitable material and the optimum pattern thickness required to maximize the fluorescence signal and maintain chemical stability was performed by confocal laser-scanning microscopy (CLSM). Results showed that the highest signal-to-background ratio was always obtained on wafers with 100 nm thick SiO₂ features. Hence, these wafers were selected for covalent binding of human AChE. Batch-wise kinetic studies revealed that enzyme activity was retained after immobilization. Combined use of atomic-force microscopy and CLSM revealed that AChE was homogeneously and selectively distributed on the SiO₂ microstructures at a suitable distance from the reflective surface. In the optimum design, efficient fluorescence emission was obtained from the AChE-based biosensing surface after labelling with propidium, a selective fluorescent probe of the peripheral binding site of AChE.

The effect of strontium dissolution by milling in water on the magnetic properties of strontium hexaferrite

The milling in or the simple contact with water of strontium hexaferrite powders produces a loss of stromtium ions which amounted to about 10% from the total amount present in ferrite when the stoichiometric compound was wet milled for 10 h. The magnetic moment of these powders decreased by as much as 10% compared to the similarly milled samples in alcohol whose chemical composition was not effected by the milling medium. The Curie temperature of the Sr deficient samples was also lower than that of the stoichiometric ones. The experimental results are discussed in terms of the modications of the superexchange interaction between the octahedral iron on the 4f and 12k sublattices, brougth about by the possible loss of oxygen atoms from the 12K sites which leave the lattice together with the Sr ions in orfer to compensate for the electric charge.     

Interpolation by positive harmonic functions

A natural interpolation problem in the cone of positive harmonicfunctions is considered and the corresponding interpolatingsequences are geometrically described.     

Development of an HPLC method for the determination of anidulafungin in human plasma and saline

An ultraviolet high-performance liquid chromatography (HPLC) method was developed to analyze anidulafungin in human plasma and saline. A reversed-phase column was used with a UV detector set at 310 nm. The mobile phase consisted of methanol and ammonium phosphate buffer at a flow rate of 1 mL/min. Micafungin was used as the internal standard. Both standard curves were linear over a range of 1 to 10 μg/mL. The intra-assay relative standard deviations (RSD) for plasma and saline matrices were 1.60-1.81% and 1.96-3.70%, respectively. The inter-assay RSD for plasma and saline matrices were 2.41-7.25% and 1.31-3.16%, respectively. This method successfully recapitulated anidulafungin plasma concentrations previously analyzed by HPLC-tandem mass spectrometry with precision and accuracy of 6.9% and 1.59%, respectively.