Synthesis of Nepsilon-protected-L-lysine and gamma-benzyl-L-glutamate N-carboxyanhydrides (NCA) by carbamoylation and nitrosation.

This paper reports on an original process to synthesize N-carboxyanhydrides, which consists of nitrosating N-carbamoylamino acids with a NO/O(2) gas mixture in acetonitrile. The synthesis of several N-carbamoylamino acids of L-lysine was described using potassium cyanate in water. The latter were then nitrosated to yield the corresponding NCA with more or less efficiency. Indeed, the NCA carrying an acid-sensitive protecting group led to a partial deprotection to give the L-lysine NCA salt. The NCA of N(epsilon)-trifluoroacetyl-L-lysine, N(epsilon)-benzyloxycarbonyl-L-lysine and gamma-benzyl-L-glutamate were successfully synthesized with satisfactory yields. Their polymerizability was compared to that of the N(epsilon)-trifluoroacetyl-L-lysine NCA initiated by n-hexylamine in N,N-dimethylformamide. It also showed that this new process of NCA synthesis could be applied to the synthesis of polypeptides and more generally to the protein chemistry.

Modification of the biocompatible and haemocompatible properties of polymer substrates by plasma-deposited fluorocarbon coatings.

The polymerization of gases present in a low temperature plasma is a technique particularly well suited for biomedical material processing. Therefore, the possibilities this technique offers to increase the biocompatibility and haemocompatibility of polysulphone and poly(hydroxybutyrate) membranes to be used in a new bioartificial pancreas device were studied. The deposition of thin fluorocarbon coatings from an argon plasma containing perfluorohexane gave very smooth and hydrophobic surfaces without affecting the filtering properties of the treated membranes. Adding hydrogen increased the reaction yield, but gave rougher and less hydrophobic coatings. We characterized the biological properties of the treated surfaces and discussed the influence of the modified surface properties on the biological behaviour of the treated polymers. The good biocompatibility of the deposited coatings was established by following in vitro the insulin secretion of Langerhans islets cultured on the treated membranes and by examining the fibrous capsule that developed on plasma-treated polymer disks after three months of in vivo incubation in the peritoneum of Wistar rats. Rough and haemocompatible films of poly(hydroxybutyrate) and smoother, but more thrombogenic, polysulphone films were treated by perfluorohexane and perfluorohexane + H2 plasmas to study the relative influence of surface roughness and surface energy on polymer thrombogenicity. In vitro protein adsorption and total blood clotting tests proved that the surface roughness influences the thrombogenicity more than the other surface properties. This study seems to show that the plasma deposition of smooth and hydrophobic fluorocarbon coatings can increase the biocompatibility and reduce the surface thrombogenicity of the treated membranes without affecting their filtering properties.

Type-I collagen production by human odontoblast-like cells in explants cultured on cyanoacrylate films. Electron-immunolocalization of fibronectin at cell/film interface.

Odontoblast-like cells derived from human tooth pulps were maintained in explant culture and grown either on glass coverslips only (used as control) or on glass coverslips coated with cyanoacrylate films. Ultrastructural and cyto-morphometric evidence showed that cells exposed to cyanoacrylate, in contrast to controls, display a significant decrease of rough endoplasmic reticulum and mitochondria. In addition, immunofluorescent staining and radioimmunoassays for type-I collagen suggested disturbances in production for the exposed cells. The use of anti-fibronectin antibodies with electron-microscopic immunoperoxidase-labelling demonstrated that the adherence of cells to cyanoacrylate can involve both adhesion plaques and fibronectin. These results therefore suggest that there were no apparent differences in the adhesion interaction of cells between glass and cyanoacrylate substrates.