Rhodopsin exhibits a preference for solvation by polyunsaturated docosohexaenoic acid

An all-atom molecular dynamics simulation of rhodopsin in a membrane environment has been carried out with lipid composition similar to that of the retinal membrane. The initial conformation of the protein was taken from the X-ray crystallographic structure (1F88), while those of the lipids came from a previous molecular dynamics simulation. During the course of the 12.5 ns simulation, the initially randomly placed lipids adopt an anisotropic solvation structure around the protein. The lipids, having one saturated stearic acid chain and one polyunsaturated docosohexaenoic acid chain with a zwitterionic phosphatidylcholine headgroup, arrange themselves to maximize contact between the polyunsaturated chain and the protein surface. This organization is driven by energetically favorable interactions between the transmembrance helices and the docosohexaenoyl chains that are largely of the van der Waals type. These observations are consistent with various experimental studies on rhodopsin and other G-protein coupled receptors and with the picture of extreme flexibility in polyunsaturated fatty acid chains that has arisen from recent NMR and computational work.     

Studies on the Chemistry of Thienoannelated O , N - and S , N -Containing Heterocycles, 28 [1]. Synthesis of Imidazo[1,5- d ]thieno[2,3- b ][1,4]thiazine Derivatives as GABA -Receptor Ligands

Summary.  GABA-receptor-ligands are still very interesting in drug-development. Usually benzodiazepines are used in the treatment but they have serious side-effects. Thus, a recently synthesized quioxaline derivative which showed reduced side-effects in an animal model was used as a model-substance. The cyclus was modified to optimize the pharmacological profile. Accordingly, a series of imidazo-thieno-thiazines was synthesized starting from 5-acetyl-2-chloro-3-nitrothiophene to yield 6-ethyl-2,3-dihydro-1H-thieno[2,3-b][1,4]thiazine-2-one. Reaction with potassium tert-butoxide and diethylchlorophosphate gave an intermediate, which resulted in the desired ring system after adding the corresponding isocyanides and potassium tert-butoxide. Corresponding author. E-mail: thomas.erker@univie.ac.at Received August 6, 2002; accepted August 13, 2002     

Beiträge zur Chemie der Pyrrolpigmente, 38. Mitt.: Zur Assoziation von Gallenpigmenten

The long standing problem of solvent dependent absorption spectra of certain bile pigments such as bilirubindimethylester has been solved by measurement of molecular masses by means of vapour pressure osmometry. Using this method and the investigation of the concentration and temperature dependence of the absorption spectra on several model compounds an association equilibrium for pigments of the rubinoid structural type could be confirmed. Moreover the optical properties of the coexisting species and the corresponding equilibrium constants could be deduced by spectroscopic techniques. Verdinoid pigments lacking free carboxylic functions on the other hand tend to be monomeric in solution. A heteroassociated species involving equimolar amounts of a verdinoid and a rubinoid pigment could be verified existing on adsorbents like silicagel.

37. Mitt.:Falk, H., Thirring, K., Tetrahedron, im Druck.     

Synthesen von Heterocyclen, 135. Mitt.: Chinolizine und Indolizine,VI: eine Synthese von 2-Hydroxy-benzo[a] chinolizin-4-onen

Zusammenfassung 2-Hydroxy-6,7-dihydro-4H-benzo[a]chinolizin-4-one (3a—p) werden durch Kondensation von 1-Alkyl-3,4-dihydro-isochinolinen (1a—g) mit Malonsäure-bis-2,4,6-trichlorphenylestern (2a—e) erhalten. Die Ausbeuten sowie die erforderlichen Reaktionszeiten und Temperaturen sind stark von der Art der Substituenten abhängig.

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Syntheses of heterocycles, CXXXV: Quinolizines and indolizines, VI. A synthesis of 2-hydroxy-4H-benzo[a]quinolizin-4-ones

The condensation of 1-alkyl-3.4-dihydro-isoquinolines (1a tog) with 2.4.6-trichlorophenyl malonates (2a—e) yields 2-hydroxy-6,7-dihydro-4H-benzo[a]quinolizin-4-ones (3a—p). Yields, required reaction-periods and temperatures are depending on the nature of the substituents present in the malonyl and isoquinoline residue.

     

Forced lattice vibrations: Part I

This is the First part of a two-part series on forced lattice vibrations in which a semi-infinite lattice of one-dimensional particles {x_n}_n≧1 is driven from one end by a particle x₀. This particle undergoes a given, periodically perturbed, uniform motion, _x0(_t) = _at + _h(_yt), where a and γ are constants and h(·) has period 2π. For a wide variety of restoring forces F (i.e., F′ > 0), numerical calculations indicate the existence of a sequence of thresholds γ₁ = γ₁(a, h, F) > γ₂ = γ₂(a,h,F) > … > γ_k = γ_k(a,h,F) > …, γ_k → 0, as k → ∞. If γ_k > γ > γ_k+1, a k-phase wave that is well described by the wave form, emerges and travels through the lattice. The goal of this series is to describe the emergence and calculate some properties of these wave forms. In Part I the authors first consider the case where F(x) = e^x (i.e., Toda forces) but h is arbitrary, and show how to compute a basic diagnostic (see J(λ), formula (1.26)) for the system in terms of the solution of an associated scalar Riemann-Hilbert problem, once a certain finite set of numbers is known. In another direction, the authors consider the case where F(x) is restoring but arbitrary, and h is small. Here the authors prove a general result, asserting that if there exists a sufficiently ample family of traveling-wave solutions of the doubly infinite lattice, then it is possible to construct time-periodic k-phase wave solutions with asymptotics in n of type (iii) for the driven system (i). In Part II, the authors prove that sufficiently ample families of traveling-wave solutions of the system (iv) exist in the cases γ > γ₁ and γ₁ > γ > γ₂ for general restoring forces F. In the case with Toda forces, F(x) = e^x, the authors prove that sufficiently ample families of traveling-wave solutions.     

Positive Lyapunov exponents for a class of deterministic potentials

LetV() be a smooth, non-constant function on the torus and letT be a hyperbolic toral automorphism. Consider a discrete one dimensional Schrödinger operatorH, whose potential at sitej is given bygV _j =gV(T ^j ). We prove that wheng0 is small andg ^1/2 |E|2–g ^1/2 , the Lyapunov exponent for the cocycle generated byH-E is proportional tog ². The proof relies on a formula of Pastur and Figotin and on symbolic dynamics.