Action de l'AMP-c sur les monocouches mixtes de céphaéline-albumine d'œuf

Résumé En vue de vérifier si l'AMP-cyclique produit une action expansive lorsqu'il agit sur les monocouches de lipoprotéines mixtes ces monocouches insolubles ont été préparées avec de la céphaéline et de l'albumine dóeuf.Ces monocouches ont montré une bonne miscibilité entre les deux composants, et seules de faibles actions réciproques ont été observées.La pénétration de l'AMP-cyclique dans ces monocouches mixtes produit un effet expansif appréciable, son action atteignant le niveau maximal lorsque la concentration de l'AMP-cyclique dans la sous-phase est de 10^–6 M (concentration normale de la cellule).Un effet similaire sur les membranes mixtes de lipoprotéines de la paroi cellulaire est attribué a l'AMP-cyclique.

---

With a view to checking whether cyclic-AMP produces an expansive action when acting on mixed lipoprotein monolayers, such insoluble monolayers were prepared with cephalin and egg albumin. These layers showed a good miscibility between the two components, with only weak interactions being observed.The penetration of cyclic-AMP in these mixed monolayers produces an appreciable expansive effect, its action reaching a maximum level when the cyclic-AMP concentration in the subphase is 10^–6 M (standard cell concentration).A similar effect on the lipoprotein mixed membranes of the cell wall is attributed to cyclic-AMP.

Directeur du Département: Prof. Dr. Serafín Garcia Fernández     

Titration microcalorimetry of poly(vinylpyrrolidone) and sodium dodecylbenzenesulphonate in aqueous solutions

Microcalorimetric titrations are carried out on solutions containing the anionic surfactant sodium dodecylbenzenesulphonate (SDBS), and mixtures of SDBS and the uncharged polymer poly(vinylpyrrolidone) (PVP). Measurements are taken at different temperatures. Micellisation of SDBS is driven by hydrophobic bonding. The interaction enthalpy of mixed PVP/SDBS systems shows clearly a consecutive endothermic and exothermic region with increasing surfactant concentration. The endothermic part can be looked upon as an incremental binding isotherm and reflects the number of surfactant molecules involved in the association process. The exothermic region features inverse hydrophobic bonding behaviour. This is related to the flexible nature of the adsorbent, i.e. the polymer. Electrostatic repulsion between neighbouring surfactant molecules causes at increased surfactant concentrations structural rearrangements of the polymer-surfactant complexes. This is accompanied by losing inter- and intrachain linking and entropy gain since the expanded complexes can move more freely. Additional surfactants continue to adsorb on the vacant hydrophobic adsorption sites. The influence of the initial amount of polymer and the electrolyte concentration support our proposals.     

Synthesis of 3,3‐Dimethylglutamic Acid Derivatives as DPP‐IV Inhibitors and Evaluation of Their Chemical Stability

A novel five‐step synthesis of Boc‐3,3‐dimethylglutamic acid α‐ethyl ester 11 is reported. All the steps are high yielding and simple to carry out. By use of the 3,3‐dimethylglutamic acid building block, we successfully discovered a novel class of DPP‐IV inhibitors, Glu‐Pro‐Nitrile dipeptide mimics 2 , with high potency (IC₅₀ < 40 nM). The consequence of 3,3‐dimethyl substituent on the rate of intramolecular cyclization between N‐terminal amine and 5‐position amide bond in different buffer solutions was also evaluated.     

Combinatorial library of peptidotriazoles: identification of [1,2,3]-triazole inhibitors against a recombinant Leishmania mexicana cysteine protease

A library consisting of about half of 800 000 possible peptidotriazoles on 450 000 beads was prepared by solid-phase peptide synthesis combined with a regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddition between a resin-bound alkyne and a protected amino azide. The central [1,2,3]-triazole was flanked on each side by two randomized amino acids introduced in a combinatorial approach. Importantly, the formation of the triazole could be performed quantitatively in a randomized fashion. The library was screened on solid phase for inhibitory effect against a recombinant cysteine protease, Leishmania mexicana CPB2.8DeltaCTE and sorted by a high-throughput instrument, COPAS beadsorter (up to 200 000 beads/h). Forty-eight hits were analyzed by MALDI-TOF MS providing structural information about the protease specificity, and 23 peptidotriazoles were resynthesized and evaluated in solution, with the best inhibitor displaying a K(i) value of 76 nM. A one-pot procedure was used to convert Fmoc-amino azides into their corresponding Boc derivatives. The crucial influence of weak interactions with a spacer used for detection by MALDI-TOF MS on screening results was observed.     

Mixed adsorption of poly(vinylpyrrolidone) and sodium dodecylbenzenesulfonate on kaolinite

The mixed adsorption of the nonionic polymer poly(vinylpyrrolidone) (PVP) and the anionic surfactant sodium dodecylbenzenesulfonate (SDBS) on kaolinite has been studied. Both components adsorb from their mixture onto the clay mineral. The overall adsorption process is sensitive to the pH, the electrolyte concentration, and the amounts of polymer and surfactant. Interpretation of the experimental data addresses also the patchwise heterogeneous nature of the clay surface. In the absence of PVP, SDBS adsorbs on kaolinite by electrostatic and hydrophobic interactions. However, when PVP is present, surfactant adsorption at 10(-2) M NaCl is mainly driven by charge compensation of the edges. The adsorption of PVP from the mixture shows similar behavior under different conditions. Three regions can be distinguished based on the changing charge of polymer-surfactant complexes in solutions with increasing SDBS concentration. At low surfactant content, PVP adsorbs by hydrogen bonding and hydrophobic interactions, whereas electrostatic interactions dominate at higher surfactant concentrations. Over the entire surfactant concentration range, polymer-surfactant aggregates are present at the edges. The composition of these surface complexes differs from that in solution and is controlled by the surface charge.     

Effect of sulphonic acid on the aqueous solubility of disperse dyes

Summary The solubilities of the following compounds in water andp-toluenesulphonic acid aqueous solution were determined at 5, 25 and 40 C: azobenzenep-aminoazobenzene,p-hydroxyazobenzene,p-N, N-dimethylaminoazobenzene and 1-phenylazo-4-aminonaphthalene. Prom the results the thermodynamic parameters for the transfer of one mole of the compound from water top-toluenesulphonic acid aqueous solution were calculated. It was found that the process was nearly athermal: furthermore, it was invariably accompanied by a positive unitary entropy change. The solubilizing mechanism of aromatic sulphonic acids was explained in terms of an adduct-formation with the compound to be dissolved by means of hydrophobic and nonpolarvan der Waals interactions.

---

Zusammenfassung Die Löslichkeiten folgender Verbindungen in Wasser und wÄ\rigerp-ToluolsulphonsÄure-Lösung wurden bei 5, 25 und 40 C bestimmt: Azobenzol,p-Aminoazobenzol,p-Hydroxyazobenzol,p-N,N-dimethylammoazobenzol undL-Phenylazo-4-aminonaphthalin. Aus den Ergebnissen wurden die thermodynamischen Parameter für den übergang eines Mols der Verbindung von Wasser zup-ToluolsulphonsÄurewÄ\rigen Lösungen berechnet. Es wurde gefunden, da\ die Prozesse nahezu athermisch sind. Au\erdem sind sie sÄmtlich durch eine positive und gleichmÄ\ig gro\e EntropieÄnderung begleitet. Der Lösungsmechanismus aromatischer SulphonsÄuren wird in den Begriffen einer Adduktbildung mit der Komponente erklÄrt, die durch die hydrophoben unpolarenvan-der-Waals-Wechselwirkungen entsteht.