Options
Neier, Reinhard
Nom
Neier, Reinhard
Affiliation principale
Fonction
Professeure ordinaire
Email
Reinhard.Neier@unine.ch
Identifiants
Résultat de la recherche
Voici les éléments 1 - 5 sur 5
- PublicationMétadonnées seulementGlycoside Esters of 5-Aminolevulinic Acid for Photodynamic Therapy of Cancer(2008)
; Juillerat-Jeanneret, LucienneAliph. and ethylene glycol esters of 5-aminolevulinic acid (ALA) are very efficient precursors of the photosensitizer protoporphyrin IX (PpIX) for photodynamic therapy; however, they diffuse passively across the cell membrane and thus lack cell selectivity. We evaluated whether ?-glucose, ?-mannose, or ?-galactose esters of ALA would present improved properties as precursors of PpIX. Esterification was performed either at the position O-1 or O-6 of the sugars with or without an ethylene glycol linker, and these glycoside esters of ALA were evaluated in human cells. The results demonstrated that glycoside esters of ALA are efficient precursors of PpIX in human cancer and angiogenic endothelial cells, comparable to free ALA, but not in normal human fibroblasts. PpIX prodn. was confirmed by fluorescence microscopy and photodynamic treatment of cells. The O-1 or O-6 positions of functionalization and the nature of the sugar moiety did not influence PpIX prodn. The presence of the ethylene glycol linker generally resulted in decreased PpIX prodn. The uptake of these glycoside esters of ALA by cells was not decreased in the presence of high concns. of the related sugars. Inhibitors of ?-glucosidases or ?-mannosidases did not decrease PpIX prodn. These results suggest the involvement of active non-glycoside-specific membrane transporter(s) for uptake and of esterases rather than glycosidases in the release of ALA from the glycoside esters of ALA. [on SciFinder(R)] - PublicationMétadonnées seulementNovel bioconjugates of aminolevulinic acid with nucleosides(2008)
- PublicationAccès libreDetermination of Intracellular Prolyl/Glycyl Proteases in Intact Living Human Cells and Protoporphyrin IX Production as a Reporter System(2005)
; Juillerat-Jeanneret, LucienneThe determination of enzyme activity or inhibition in intact living cells is a problem in the development of inhibitors for intracellular proteases. The production of fluorescent protoporphyrin IX (PpIX) from the nonfluorescent (N)-Gly/Pro-5-aminolevulinic acid (ALA) substrates was used to evaluate the prolyl/glycyl-specific dipeptidylpeptidase IV (DPPIV)-like and prolyloligopeptidase (POP)-like activities of human cells. The results demonstrated that whereas POP-like activity could be attributed to the actual POP, the DPPIV-like activity could be related to actual DPPIV only in one colon cell line. In the other breast and colon cell lines, DPPIV-like activity was intracellular and displayed by other prolyl-specific aminopeptidases. Our experiments also demonstrated the involvement of gylcyl-specific proteases in the processing of ALA precursors. These observations have important consequences for the development and evaluation of selective inhibitors for these enzymes. - PublicationAccès libreEvaluation of dipeptide-derivatives of 5-aminolevulinic acid as precursors for photosensitizers in photodynamic therapy(2003)
; Juillerat-Jeanneret, LucienneN-terminal-blocked and N-terminal-free pseudotripeptide Gly-Gly and Gly-Pro derivatives of 5-aminolevulinic acid (ALA) esters were synthesized as potential specific substrates for cellular peptidases and precursors for the production of the photosensitizer protoporphyrin IX (PpIX). These precursors were evaluated using human cell lines of either carcinoma or endothelial origin. N-blocked or N-free dipeptides-ALA-ethyl esters, but not tripeptides-ALA-ethyl esters (or dipeptides-ALA-ethyleneglycols,) were substrates for cellular peptidases and were metabolized to ALA. The precursors were hydrolyzed intracellularly involving serine-proteases and metalloproteases. Cell selectivity for human endothelial or carcinoma cells was observed for some of these dipeptides-ALA. Thus drugs coupled to Gly-Gly-/Gly-Pro-derivatives may selectively target defined cells in human cancer, depending on specific cellular activating pathways expressed by the cells. - PublicationMétadonnées seulementEthylene glycol and amino acid derivatives of 5-aminolevulinic acid as new photosensitizing precursors of protoporphyrin IX in cells(2000)
; Juillerat-Jeanneret, LucienneProtoporphyrin IX (PpIX) is used as a photosensitizing agent in photodynamic detection and therapy (PDT) of cancer and is synthesized intracellularly from aminolevulinic acid (ALA) precursors. To evaluate means to specifically target ALA derivatives to defined cells, we have synthesized and characterized ethylene glycol esters and amino acid pseudodipeptide derivatives of ALA as potential specific substrates for cellular esterases and aminopeptidases, respectively. The PpIX formation induced by these products was investigated using cultures of human and rat cell Lines of carcinoma and endothelial origins. The cytotoxicity of these compounds in the absence of light was also controlled. The results have shown that ethylenglycol esters can induce high levels of PpIX and are useful at concentrations below their cytotoxicity threshold. From the ALA-amino acid derivatives which were evaluated, the highest PpIX production was obtained using ALA derivatives of neutral amino acids, as compared to acidic or basic amino acids.