Direct interaction between an allosteric agonist pepducin and the chemokine receptor CXCR4

Cell surface heptahelical G protein-coupled receptors (GPCRs) mediate critical cellular signaling pathways and are important pharmaceutical drug targets. (1) In addition to traditional small-molecule approaches, lipopeptide-based GPCR-derived pepducins have emerged as a new class of pharmaceutical agents. (2, 3) To better understand how pepducins interact with targeted receptors, we developed a cell-based photo-cross-linking approach to study the interaction between the pepducin agonist ATI-2341 and its target receptor, chemokine C-X-C-type receptor 4 (CXCR4). A pepducin analogue, ATI-2766, formed a specific UV-light-dependent cross-link to CXCR4 and to mutants with truncations of the N-terminus, the known chemokine docking site. These results demonstrate that CXCR4 is the direct binding target of ATI-2341 and suggest a new mechanism for allosteric modulation of GPCR activity. Adaptation and application of our findings should prove useful in further understanding pepducin modulation of GPCRs as well as enable new experimental approaches to better understand GPCR signal transduction.     

A sulfone-based strategy for the preparation of 2,4-disubstituted furan derivatives

2,4-Disubstituted furans are prepared by treating 2,3-dibromo-1-phenylsulfonyl-1-propene (DBP, 2) with 1,3-diketones under basic conditions. The furan-forming step involves a deacetylation, and the selectivity of this process depends upon the steric demand of the R group. The substituent in position 4 is elaborated by reaction of sulfonyl carbanions with alkyl halides, acyl halides, and aldehydes. Oxidative or reductive desulfonylation produces the 2,4-disubstituted furans in 60-92% yield. This strategy has been used to prepare rabdoketone A (12) and the naturally occurring nematotoxic furoic acid 13.     

Equation of state of CaMnO3: a combined experimental and computational study

Elastic properties of CaMnO₃ are of primary importance in the science and technology of CaMnO₃-based perovskites. From X-ray diffraction experiments performed at pressures up to 100 kbar using a diamond-anvil cell to hydrostatically compress our sample, a bulk modulus, K ₀, of 1734(96) kbar was obtained after fitting parameters to the third-order Birch–Murnaghan equation of state. Mean field, semiclassical simulations predict, for the first time, the third-order equation-of-state parameters and show how the bulk modulus increases with pressure (the zero pressure value being 2062.1 kbar) and decreases with the extent of nonstoichiometry caused by the formation of oxygen vacancies. These trends are amplified for the shear modulus. A more accurate model that allows for the explicit reduction of Mn ions, or localization of excess electrons, yields qualitatively similar results. The experimental and calculated axial ratios show the same trends in their variation with rising pressure.     

Nachweis und Bestimmung der Halogensauerstoffverbindungen

Ohne Zusammenfassung     

Day-side auroral signatures based on simultaneous, coordinatedobservations at Svalbard and Greenland

The height distribution of the dayside cusp aurora and the relation between optical emissions and net downward electron energy flux are discussed. These two important characteristics of day-side cusp aurora are still unknown. It is instructive to compare particle flux and optical luminosity because these two quantities should be proportional if the cusp aurora is caused by electron impact, as has been found for nighttime aurora in the oval. Furthermore, there should then be a direct relation between auroral altitudes and particle energy. Based on coordinated auroral observations at Svalbard and Greenland, together with simultaneous, overhead F-9 satellite measurements, these quantities have been evaluated     

An Observation on Two Methods of Obtaining Solutions to Variational Problems

In this paper, we compare two methods for obtaining solutions for free problems in the calculus of variations. The first is due to Carathéodory (Ref. 1) and the second due to Leitmann (Ref. 2). Both methods introduce the notion of equivalent variational problems. Using either approach, an auxiliary problem is obtained for which the solution is more easily obtained. We compare both approaches by using each to solve the same class of examples. We conclude our discussion by unifying the two approaches into one and illustrating the potential of this new method through the use of an elementary example.     

Coordinate Transformation Method for the Extremization of Multiple Integrals

In this paper, we generalize a coordinate transformation method, due to Leitmann (Ref. 1), for free problems in the calculus of variations to analogous problems with multiple integrals.