alpha-conotoxins PnIA and [A10L] PnIA stabilize different states of the alpha 7-L247T nicotinic acetylcholine receptor

The effects of the native alpha-conotoxin PnIA, its synthetic derivative [ A10L] PnIA and alanine scan derivatives of [ A10L] PnIA were investigated on chick wild type alpha7 and alpha7-L247T mutant nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes. PnIA and [A10L] PnIA inhibited acetylcholine (ACh)-activated currents at wtalpha7 receptors with IC50 values of 349 and 168 nM, respectively. Rates of onset of inhibition were similar for PnIA and [ A10L] PnIA; however, the rate of recovery was slower for [ A10L] PnIA, indicating that the increased potency of [ A10L] PnIA at alpha7 receptors is conveyed by its slower rate of dissociation from the receptors. All the alanine mutants of [ A10L] PnIA inhibited ACh-activated currents at wtalpha7 receptors. Insertion of an alanine residue between position 5 and 13 and at position 15 significantly reduced the ability of [ A10L] PnIA to inhibit ACh-evoked currents. PnIA inhibited the non-desensitizing ACh-activated currents at alpha7-L247T receptors with an IC50 194 nM. In contrast, [ A10L] PnIA and the alanine mutants potentiated the ACh-activated current alpha7-L247T receptors and in addition [ A10L] PnIA acted as an agonist. PnIA stabilized the receptor in a state that is non-conducting in both the wild type and mutant receptors, whereas [ A10L] PnIA stabilized a state that is non-conducting in the wild type receptor and conducting in the alpha7-L247T mutant. These data indicate that the change of a single amino acid side-chain, at position 10, is sufficient to change the toxin specificity for receptor states in the alpha7-L247T mutant.

Solubility of selected esters in supercritical carbon dioxide

The solubility of ethyl propionate, ethyl butyrate, and ethyl isovalerate in supercritical carbon dioxide was measured at temperature ranging from 308.15 to 333.15 K and pressure ranging from 85 to 195 bar. At the same temperature, the solubility of these compounds increases with pressure. The crossover pressure region was also observed in this study. The experimental data were correlated by the semi-empirical Chrastil equation and Peng-Robinson equation of state (EOS) using several mixing rules. The Peng-Robinson EOS gives better solubility prediction than the empirical Chrastil equation. (C) 2002 Elsevier Science B.V. All rights reserved.

Synthesis of novel 2-amino-1,3-thiazole-5-carboxylates utilising ultrasonic and thermally mediated aminolysis

Novel 2-amino-1,3-thiazole-5-carboxylates have been synthesised in high yield by unprecedented ultrasonic and thermally mediated nucleophilic displacement of bromide from ethyl 2-bromo-1,3-thiazole-5-carboxylate by primary, secondary and aryl amines.

The synthesis and X-ray crystal structure of 9-carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one

9-Carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one (1) was prepared and examined by X-ray crystallography to probe its potential as a new peptide scaffold/template. The crystal structure of the anhydride precursor 7-(2-acetoxyethyl)-4-methoxy-3a,4,7,7a-tetrahydro-4,7-ethanoisobenzofuran-1,3-dione (6) is also reported.