A conformational basis for the selective action of ara-adenine.
Explore the source record for details and available documents.
Adenosine Kinase↗
Biomedical subjects
H Eyring
Publications and source records attributed to H Eyring.
Significant structure theory applied to phase separation.
The significant structure theory of liquids has been applied to the partially miscible system of the O(3)-O(2) mixture, which exhibits partial miscibility in the temperature range from -195.5 degrees C to -179.9 degrees C. The thermodynamic condition for phase separation is given by the following inequality: [Formula: see text] A partition function for the binary liquid mixture is developed using significant liquid structure theory. Here X(i) is the mole fraction of either of the two components. We obtain the coexistence curve of the O(3)-O(2) system by varying the mole fractions of the components to find the temperature at which the two liquids separate. The agreement between theory and experiment is satisfactory.
Journal Article↗
Significant structure theory applied to liquid helium-3.
The significant structure theory of liquids is successfully applied to the quantum liquid (3)He. The partition function uses the Debye partition function for the solid-like molecules and the Fermi-Dirac partition function for the gas-like degrees of freedom. To evaluate the gas-like partition function, numerical calculations are performed and some integral functions appearing in the equation of state of the ideal Fermi-Dirac gas are tabulated. In the solid-like molecules, the molar volume V(s) depends on the temperature, and a linear dependence is used.The thermodynamic properties, such as molar volume, vapor pressure, entropy, heat capacity, and the critical constants as well as the surface tension of liquid (3)He are calculated. The agreement between theory and experiment is satisfactory.
Journal Article↗
Reversible and irreversible inhibition by anesthetics of the calcium-induced luminescence of aequorin.
The actions of various kinds of so-called membrane-stabilizing drugs on Ca2+-induced flash intensity of purified aequorin, a photoprotein obtained from Aequorea aequorea, were examined. All drugs used in this experiment, including inhalational anesthetics, tetracaine, chlorpromazine, and morphine, depressed flash intensity, and the inhibition increased with time. The inhibition followed a mixture of reversible and irreversible kinetics. A method of analyzing irreversible kinetics is presented. The dissociation constants for reversible inhibition and the rate constants for irreversible inhibition are presented for each agent.
Aequorin↗
Circular dichroism of adenosine dinucleotides.
The circular dichroism and absorption spectra of (3'-5')ApA, (5'-5')AppA, and (5'-5')ApcpA [diadenosine(5'5') pyrophosphonate] under various ionic coditions and at various temperatures are reported. Temperature studies reveal that under the same ionic strength and solvation conditions the probability of base-base interaction is ApA greater than AppA greater than ApcpA. It is found that increasing the molar refractivity of the solvent decreases the base-base interaction for both ApA and AppA and that both compounds proceed to a monomeric state in solvents of high molar refractivity. Solvent effect studies also indicate that a major percentage of the driving force for the base-base interaction can be accounted for by London dispersion forces. Low ionic strength appears to favor the base-base interacted conformation. All compounds tend toward the same noninteracted form at high temperatures. Plots of [theta]lambda against X (where X is an experimental parameter) were constructed in order to obtain information concerning which transitions might be undergoing oscillator coupling. To a first approximation, transitions coupled to each other should have very similar deta[theta]lambda/detaX for the experimental range of X. Applying this technique to the experimental data yielded information concerning possible transition coupling.
Adenine Nucleotides↗
Conformational basis for the activation of adenylate cyclase by adenosine.
The ability of adenosine to stimulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and increase adenosine 3':5'-cyclic monophosphate (cAMP) levels has important biochemical consequences. These include the suppression of immune responses and cardiovascular effects. Recent investigations involving the ability of adenosine and adenosine analogs to stimulate adenylate cyclase provided experimental data that appear to be correlated with the ability of adenosine and analogs of adenosine to exist in the glycosidic high anti conformation. 9-beta-D-Arabinofuranosyladenine, which is not stable in the high anti conformation, is inactive as a stimulator of adenylate cyclase. 2'-Deoxyadenosine is also not stable in the high anti conformation but its instability may be significantly decreased by intramolecular adjustments promoted by receptor or active site interactions. 2'-Deoxyadenosine does not activate adenylate cyclase in lymphocytes when ATP is the substrate but is able to activate adenylate cyclase when 2-fluoro ATP is the substrate. The inability of certain analogs of adenosine, with bulky groups substituted for hydrogen at the 8 position of the adenine base, to activate adenylate cyclase and increase either lymphocyte or cardiac cell cAMP levels is consistent with the designation of the high anti conformation as being the conformation required for the activation of adenylate cyclase. An understanding of the glycosidic conformation required by the extracellular adenosine receptor of the adenosine molecule provides the basis for designing nucleoside analogs of adenosine that will exert a desired effect on cAMP levels. The avoidance of unwanted immunosuppressive or cardiotoxic effects can be arranged by structural changes that prohibit the high anti conformation.
Adenosine↗
Single partition function for three phases.
The significant structures theory of liquids has been extended to take into account (i) translational degrees of freedom in the degeneracy term and (ii) the perturbation term which becomes important near the critical region. With these improvements, the calculated thermodynamic properties of argon agree very well with experimental results from the melting point through the critical point, along the coexistence curve as well as along the critical isochore and for the solid and the vapor.
Journal Article↗
Quantum statistical theory of optical phenomena.
The purpose of this paper is to develop a density matrix formulation for optical phenomena that can be applied to both steady and transient states and to both resonance and off-resonance regions. To demonstrate the application, this theory has been applied to the steady-state one-photon and two-photon processes. We have found that, in the resonance region, the conventional equation used is incomplete; other terms that are comparable in importance have been ignored.
Journal Article↗
A general treatment of relaxation phenomena.
The singular perturbation method has been applied to solve the quantum mechanical Liouville equation for the relaxation phenomenon of the system in thermal contact with a heat bath. The master equation derived gives the proper expressions for both diagonal and off-diagonal elements of the density matrix and is capable of describing the time-dependent behavior of the system in the time range comparable with the reciprocal of the damping constants and the time range t --> infinity compared with the reciprocal of the damping constants.
Journal Article↗
Multiple factor analysis of the action of local anesthetics.
The pH jump data of Bianchi and Strobel [(1968) Trans. N.Y. Acad. Sci. Ser. II, 30, 1082-1092] on desheathed frog sciatic nerve are fitted to rate equations. A general quantitation of synergism, summation, and antagonism of anesthetics and of excitation is given.
Action Potentials↗
Nuclear magnetic resonance studies of the interaction of general anesthetics with 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine bilayer.
Sonicated 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine forms liposomes. Studies by Fourier transform proton magnetic resonance of the interaction of these bilayers with some general anesthetics, i.e., chloroform, halothane, methoxyflurane, and enflurane, show that the addition of a general anesthetic to the liposomes and raising the temperature have a similar effect in cuasing the fluidization of the bilayer. General anesthetics act on the hydrophilic site (choline group) in clinical concentrations and then diffuse into the hydrophobic region with the addition of larger amount of anesthetics. There is evidence that the lecithin choline groups are involved in the interaction with protein and that the general anesthetics change the conformation of some polypeptides and proteins. We conclude that the general anesthetics, by increasing the motion of positively charged choline groups and negatively charged groups in protein, weaken the Coulomb-type interaction and cause the liprotein conformational changes.
Anesthetics↗
Theoretical studies of the conformational properties of ribavirin.
One of the factors required for the antiviral activity of the synthetic nucleoside, ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), is the ability of the molecule to adopt the substrate conformation specified by the enzyme for which it is a competitive inhibitor, inosine 5'-phosphate dehydrogenase (IMP:NAD+ oxidoreductase, EC 1.2.1.14). The calculated glycosidic minimum for ribavirin is the high syn conformation, which is in agreement with experimental determinations of the molecule's solution conformation. The similarity in solution between the conformation of the active ribavirin molecule and the conformation of its inactive 5-methyl and 5-chloro derivatives indicate that some other substrate conformation is specified by the enzyme. The high anti conformation, found by these calculations to be close in energy to the high syn minimum, is postulated to be the active conformation required by the enzyme. The inactivity of the 5-methyl and 5-chloro derivatives is attributed to the much greater stability of these derivatives in the inactive high syn conformation.
Binding Sites↗
Molecular mechanism of inhibition of firefly luminescence by local anesthetics.
The kinetics of the action of local anesthetics upon firefly luciferin and luciferase systems is presented. Clinical concentrations of local anesthetics inhibited this ATP-induced luminescence in a dose-dependent manner. From the effects of temperature and pH upon the inhibitory action of the local anesthetics, it is concluded that hydrophobic ligand-enzyme interaction is the predominant cause of the inhibition, but hydrophilic interaction also contributes to the inhibition to a lesser degree. A molecular theory of anesthesia is outlined which postulates that release of electrostricted water molecules from the hydrophilic parts of the enzyme due to the protein conformational changes induced by anesthetics is the cause of the decreased luminescence. A similar mechanism is expected to occur at the cell membrane, which probably dehydrates the sodium channel and suppresses the conductance of this ion across the membrane. These events lead to a volume expansion of the total system, and the system becomes reactive to a pressure which reverses the anesthesia by shifting the equilibrium to the nonanesthetized original volume. The pressure antagonism of anesthesia can be explained by this overall volume expansion and not by a mere swelling of the cell membrane.
Anesthetics, Local↗
Combined effects of dissociable and undissociable local anesthetics upon ATP-induced firefly bioluminescence.
Combined effects of two drugs present simultaneously are usually expressed as summation, synergism or potentiation, and antagonism. When the sum of the effects of each drug present separately equals the combined effect of the two drugs present simultaneously, the action is called additive or summation. However, the expected value of the sum of each effect of drugs present alone has not been well defined. In this report, the thearetical value of the expected sum of each effect of two inhibitors is given and a graphical method is presented to visualize summation, synergism, and antagonism. The inhibitory effects of a dissociable local anesthetic, tetracaine, and an undissociable local anesthetic, benzyl alcohol, upon a soluble firefly luminescent system were analyzed according to the above theory. The results clearly indicate that the action of these two classes of local anesthetics is pure additive or summation.
Adenosine Triphosphate↗
Comparative study by circular dichroism of the conformation of deazapurine nucleosides and that of common purine nucleosides.
Purine nucleoside analogs modified by replacement of the nitrogen atom at the 3 position by a CH group give a characteristic circular dichroism curve that is not substantially modified by chemical substitution at the 8 position. Since it is rather well established that 8-substituted purine nucleosides are predominantly in the syn conformation in aqueous solution, it follows that the 3-deazapurine nucleosides, whether substituted at position 8 or not, also favor the syn conformation. These data are in sharp contrast to the circular dichroism data obtained on 8-halogenated and 8-alkylated derivatives of adenosine and guanosine, which give circular dichroism profiles substantially different from those obtained on the parent compounds. Certain purine-nucleoside-utilizing enzymes fail to interact effectively with either the unsubstituted 3-deaza analogs or the 8-substituted derivatives of adenosine and guanosine. The hypothesis recently given that the inactivity of the 8-substituted derivatives springs from their syn-conformational preference is tentatively accepted to explain the inactivity of the 3-deaza analogs.
Adenosine↗
Medium-induced radiationless transitions and effect of solvent on radiationless transitions.
The purpose of this paper has been to investigate the effect of solvent on radiationless transitions. Two types of the solvent effect have been studied: one is the so-called medium-induced radiationless transition, i.e., the radiationless transition induced by the interaction between the solute and solvent, and the other is the effect of solvent on the radiationless transition through the change in energy gap induced by the solute-solvent interaction.
Journal Article↗
Magnetic circular dichroism of molecules in dense media: Spin-forbidden transitions of carbonyl molecules.
The purpose of this paper has been to calculate the magnetic rotational strength of the spin-forbidden (1)A(1) --> (3)A(2) transition of the carbonyl group. For this purpose, simple molecular orbitals have been used and only one-center integrals have been considered. The calculated results have been compared with the experimental measurements.
Journal Article↗
The significant structure theory applied to a mesophase system.
The significant structure theory of liquids is extended to the mesophase system with p-azoxyanisole as an example. This compound has two different structures, a nematic phase and an isotropic phase, in its liquid state. In this study the nematic phase is treated as subject to a second volume and temperature-dependent degeneracy formally like that due to melting. The isotropic phase is treated as a normal liquid. The specific heat, thermal expansion coefficient, compressibility, volume, entropy of transitions, and heat of transitions are calculated and compared to the observed values. This analysis differs from previous ones in including the volume dependence as well as the temperature dependence in one explicit expression for the Helmholtz free energy.
Journal Article↗