Laurent Mauclaire

Physico-chemical investigation of asymmetrical peptidolipidyl-cyclodextrins.

A new class of amphiphilic peptidolipidyl-cyclodextrins is reported. The derivatives are chiral due to the presence of an L-leucine in the spacer arm that links a saccharide moiety and a grafted, saturated hydrocarbon chain. Self-assembly properties of the peptidolipidyl-cyclodextrins are characterized by quasi-elastic light scattering, turbidity and UV-visible absorption measurements. NMR experiments give insight into the intermolecular dipolar interactions as a function of temperature and concentration. N-dodecyl-N alpha-(6 I-amidosuccinyl-6 1-deoxy-cyclomaltoheptaose)-L-leucine (1) is poorly soluble in aqueous media. N-dodecyl-N(alpha)-(6 I-amidosuccinyl-6 I-deoxy-2 I,3 I-di-O-methyl-hexakis-(2 II-VII,3 II-VII,6 II-VII-tri-O-methyl)-cyclomaltoheptaose)-L-leucine (2) is found to be more soluble and self-assembles into stable supramolecular colloidal aggregates with nanometric dimensions above a critical aggregation concentration (CAC). It has a propensity for solubilization of hydrophobic species revealing a micellar-like behavior, which is compared to that of the non-ionic detergent octyl glucoside. On the contrary, compound 1 precipitates in a crystalline phase beyond its water solubility limit, and it does not display any solubilizing capacity. The observed behavior corroborates at the molecular level with the NMR results.

Iodolisuride and iodobenzamide, two ligands for SPECT exploration of the dopaminergic D2 receptors: A comparative study

Iodobenzamide (IBZM) and iodolisuride (ILIS), which belong to different chemical families, are two radioligands used for SPECT imaging of dopamine D2 receptors. We have compared their cerebral biodistribution in control rats and their ability to detect quantitative modifications of D2 receptors in experimental models. IBZM and ILIS have a similar cerebral distribution in vivo in control rats and permitted the detection of upregulation of striatal dopamine D2 receptors in a model of chronic haloperidol treatment. Moreover, we observed that 1 h after injection of a saturating dose of haloperidol, IBZM uptake was 72% displaced from the striatum, while ILIS uptake was 50% displaced. In an experimental model of excitotoxic striatal lesion, the in vivo accumulation of IBZM was 30% decreased on the lesioned side, in agreement with a decrease in dopamine D2 receptor density. By contrast, the accumulation of ILIS was identical in the lesioned and in the intact striatum. From the results, it appears that IBZM and ILIS, which are both used to image dopamine D2 receptors in vivo, behave differently in pathological experimental models. The ligand for human exploration should then be chosen according to the suspected pathology.

Synthesis of porphyrins with pendant arms: Participation of the ancillary ligands to the complexation process in proteic medium

Abstract Ortho substituted porphyrins are able to complex copper (+II) in a neutral aqueous medium containing an excess of bovine albumine.

New preparation of (123I) iodolisuride from the 2-tri-n-butylstannalisuride derivative

Abstract A simplified and efficient method is described for the preparation of [ 123 I]2-iodolisuride. The radioiodination of 3-(9,10-didehydro-6methyl-8a-ergolinyl)-1,1-diethylurea (lisuride) is based on tributyltin to 123 I exchange in oxidative conditions. After optimization of the reaction parameters [ 123 I]2-iodolisuride was obtained without high performance liquid chromatography purification with radiochemical yields >90% and a radiochemical purity higher than 95%. The specific activity of the product was more than 500 MBq/nmol. In vitro binding studies on striatal membranes and ex vivo autoradiography in rats showed that [ 123 I] or [ 125 I]2-iodolisuride prepared using this method, have the same radiopharmacological characteristics as radioiodinated iodolisuride prepared using the Iodogen® method.