Absolute Configuration of Two New 6‐Alkylated α‐Pyrones (=2H‐Pyran‐2‐ones) from Ravensara crassifolia

The stem bark CH₂Cl₂ extract of Ravensara crassifolia showed antifungal activity against the phytopathogenic fungus Cladosporium cucumerinum in a bioautographic TLC assay. Activity‐guided fractionation afforded two new α‐pyrones : (6S)‐5,6‐dihydro‐6‐[(2R)‐2‐hydroxy‐6‐phenylhexyl]‐2H‐pyran‐2‐one ( 1 ) and (6R)‐6‐[(4R,6R)‐4,6‐dihydroxy‐10‐phenyldec‐1‐enyl]‐5,6‐dihydro‐2H‐pyran‐2‐one ( 2 ). Their structures and absolute configurations were established by NMR spectroscopy, chemical methods, and CD spectroscopy. The antifungal activity against C. cucumerinum was determined for both compounds.     

DSC examination of intestinal tissue following warm ischemia and reperfusion injury

The fact that small bowel is extremely sensitive to ischemia/reperfusion (I/R) injury had encouraged us to compare the conventional histology and differential scanning calorimetry (DSC) methods in intestinal structural changes following experimental warm I/R models. Our histological findings showed that longer warm I/R period caused more severe damage in structure of mucosa and crypts, but there were no changes in the muscular layer. According to our DSC data (transition temperature, calorimetric enthalpy) suggest that the thermal destruction of mucosa, muscular layer and total intestinal wall following I/R injury revealed significant differences compared to normal bowel structure.     

Hot spot analysis for driving the development of hits into leads in fragment-based drug discovery

Fragment-based drug design (FBDD) starts with finding fragment-sized compounds that are highly ligand efficient and can serve as a core moiety for developing high-affinity leads. Although the core-bound structure of a protein facilitates the construction of leads, effective design is far from straightforward. We show that protein mapping, a computational method developed to find binding hot spots and implemented as the FTMap server, provides information that complements the fragment screening results and can drive the evolution of core fragments into larger leads with a minimal loss or, in some cases, even a gain in ligand efficiency. The method places small molecular probes, the size of organic solvents, on a dense grid around the protein and identifies the hot spots as consensus clusters formed by clusters of several probes. The hot spots are ranked based on the number of probe clusters, which predicts the binding propensity of the subsites and hence their importance for drug design. Accordingly, with a single exception the main hot spot identified by FTMap binds the core compound found by fragment screening. The most useful information is provided by the neighboring secondary hot spots, indicating the regions where the core can be extended to increase its affinity. To quantify this information, we calculate the density of probes from mapping, which describes the binding propensity at each point, and show that the change in the correlation between a ligand position and the probe density upon extending or repositioning the core moiety predicts the expected change in ligand efficiency.     

Structural transitions induced by shear flow and temperature variation in a nonionic surfactant/water system

In this study, we investigate structural transitions of tetraethylene glycol monohexadecyl ether (C(16)E(4)) in D(2)O as a function of shear flow and temperature. Via a combination of rheology, rheo-small-angle neutron scattering and rheo-small-angle light scattering, we probe the structural evolution of the system with respect to shear and temperature. Multi-lamellar vesicles, planar lamellae, and a sponge phase were found to compete as a function of shear rate and temperature, with the sponge phase involving the formation of a new transient lamellar phase with a larger spacing, coexisting with the preceding lamellar phase within a narrow temperature-time range. The shear flow behavior of C(16)E(4) is also found to deviate from other nonionic surfactants with shorter alkyl chains (C(10)E(3) and C(12)E(4)), resembling to the C(16)E(7) case, of longer chain.     

Testing of innovative materials for medical additive manufacturing by DTA

Journal of Thermal Analysis and Calorimetry - Additive manufacturing technologies revolutionize many aspects of our everyday life. Biomedical applications benefit a lot from 3D printing. From...     

The chemistry of 2H-3,1-benzoxazine-2,4-(1H)dione (isatoic anhydride) 3. One step synthesis of 2,3-dihydro-4,1,6-benzoxadiazonine-5,7-(1H,6H)diones

Reactions of N-haloalkylisatoic anhydrides with amines to produce piperidinobenzamides ( 2 ), pyrrolidinobenzamides ( 4 and 5 ), and 2,3-dihydro-6-methyl-4,1,6-benzoxadiazonine-5,7-(1H,6H)diones ( 10 ) are described. Spectral data are also discussed.     

Finite-state and reduced-parameter representations of protein backbone conformations

This article studies the representation of protein backbone conformations using a finite number of values for the backbone dihedral angles. We develop a combinatorial search algorithm that guarantees finding the global minima of functions over the configuration space of discrete protein conformations, and use this procedure to fit finite-state models to the backbones of globular proteins. It is demonstrated that a finite-state representation with a reasonably small number of states yields either a small root-mean-square error or a small dihedral angle deviation from the native structure, but not both at the same time. The problem can be resolved by introducing limited local optimization in each step of the combinatorial search. In addition, it is shown that acceptable approximation is achieved using a single dihedral angle as an independent variable in local optimization. Results for 11 proteins demonstrate the advantages and shortcomings of both the finite-state and reduced-parameter approximations of protein backbone conformations. © 1994 by John Wiley & Sons, Inc.