Small molecule antagonists of cell-surface heparan sulfate and heparin–protein interactions

Surfen, bis-2-methyl-4-amino-quinolyl-6-carbamide, was previously reported as a small molecule antagonist of heparan sulfate (HS), a key cell-surface glycosaminoglycan found on all mammalian cells. To generate structure–activity relationships, a series of rationally designed surfen analogs was synthesized, where its dimeric structure, exocyclic amines, and urea linker region were modified to probe the role of each moiety in recognizing HS. An in vitro assay monitoring inhibition of fibroblast growth factor 2 binding to wild-type CHO cells was utilized to quantify interactions with cell surface HS. The dimeric molecular structure of surfen and its aminoquinoline ring systems was essential for its interaction with HS, and certain dimeric analogs displayed higher inhibitory potency than surfen and were also shown to block downstream FGF signaling in mouse embryonic fibroblast cells. These molecules were also able to antagonize other HS–protein interactions including the binding of soluble RAGE to HS. Importantly, selected molecules were shown to neutralize heparin and other heparinoids, including the synthetic pentasaccharide fondaparinux, in a factor Xa chromogenic assay and in vivo in mice. These results suggest that small molecule antagonists of heparan sulfate and heparin can be of therapeutic potential for the treatment of disorders involving glycosaminoglycan–protein interactions.     

Synthesis by Si-H bond lithiation of novel half-pincer and pincer silyllithium compounds and their molecular structures

Structural Chemistry - The synthesis and the X-ray structural analysis of novel pincer and half-pincer silyllithiums: Ar2 (N)(tBu2MeSi)SiLi (Ar(N) = o-dimethylbenzylamine) (2a),...     

Isothermal titration calorimetry as a new tool to investigate chiral interactions at crystal surfaces

In this communication we describe for the first time the use of isothermal titration calorimetry (ITC) to measure the energetics of adsorption of enantiomers from aqueous onto chiral crystal surfaces. Our results demonstrate that ITC can be used to measure chiral interactions at crystal surfaces.     

Conglomerate crystallization on self-assembled monolayers

In this communication, we demonstrate that chiral self-assembled monolayers can be used for polymorphism control of chiral crystals. We studied the crystallization of DL-glutamic acid on chiral self-assembled monolayers and showed that crystallization of DL-glutamic acid on the chiral SAMs resulted in stabilization of the metastable conglomerate form.     

Durability of polyurethanes elastomers

The effect of thermal aging on three different elastomeric polyurethane adhesives was studied. Consequently, an attempt was made to predict the polyurethanes' service lifetimes from the changes in tensile properties, hardness of bulk specimens and adhesion strength properties (lap shear and butt joints) of polycarbonate bonded joints. Aging temperatures ranged from ambient to 70 °C (at 50% relative humidity) for durations from 20 days to 18 months. Experimental results were analyzed according to a kinetic rate theory and using limit values for the various properties. Consequently, service lifetimes were determined and compared to results from actual service life. Predictions of long-term performance from accelerated tests proved to be reasonable for the properties and materials studied.     

On spectral analysis in locally compact motion groups

Beurling's theorem in spectral analysis of bounded functions on the real line is generalized to a class of locally compact motion groups and to Heisenberg groups.     

Fully symmetric integration rules for the 4-cube

In this paper we discuss fully symmetric integration rules of degree 7 and 9 for the 4-cube. In particular we are interested in good rules. (i.e. rules with all the evaluation points inside the cube and all the weights positive).This work was supported by the Norwegian Research Council for Sciences and Humanities.     

Spectrofluorometric Determination of Hydrogen Peroxide

A Spectrofluorometric method for microdetermination of H₂O₂ has been developed. The method is based on the oxidation of hydrogen peroxide with ceric ion in acid solution and measurement of the fluorescence during titration of the Ce(III) ions produced. The fluorescent species have excitation and emission maxima at 260 and 360 nm, respectively. The detection limit of measurement by this method was 0.1 ppm hydrogen peroxide.     

Ferrioxamine B analogues: targeting the FoxA uptake system in the pathogenic Yersinia enterocolitica

A series of ferrioxamine B analogues that target the bacterium Yersinia enterocolitica were prepared. These iron carriers are composed of three hydroxamate-containing monomeric units. Two identical monomers consist of N-hydroxy-3-aminopropionic acid coupled with beta-alanine, and a third unit at the amino terminal is composed of N-hydroxy-3-aminopropionic acid and one of the following amino acids: beta-alanine (1a), phenylalanine (1b), cyclohexylalanine (1c), or glycine (1d). Thermodynamic results for representatives of the analogues have shown a strong destabilization (3-4 orders of magnitude) of the ferric complexes with respect to ferrioxamine B, probably due to shorter spacers and a more strained structure around the metal center. No significant effect of the variations at the N-terminal has been observed on the stability of the ferric complexes. By contrast, using in vivo radioactive uptake experiments, we have found that these modifications have a substantial effect on the mechanism of iron(III) uptake in the pathogenic bacteria Yersinia enterocolitica. Analogues 1a and 1d were utilized by the ferrioxamine B uptake system (FoxA), while 1b and 1c either used different uptake systems or were transported to the microbial cell nonspecifically by diffusion via the cell membrane. Transport via the FoxA system was also confirmed by uptake experiments with the FoxA deficient strain of Yersinia enterocolitica. A fluorescent marker, attached to 1a in a way that did not interfere with its biological activity, provided additional means to monitor the uptake mechanism by fluorescence techniques. Of particular interest is the observation that 1a was utilized by the uptake system of ferrioxamine B in Yersinia enterocolitica (FoxA) but failed to use the ferrioxamine uptake route in Pseudomonas putida. Here, we present a case in which biomimetic siderophore analogues deliberately designed for a particular bacterium can distinguish between related uptake systems of different microorganisms.