Abstract |
N-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.
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Authors | Yann Berger, Laurent Ingrassia, Reinhard Neier, Lucienne Juillerat-Jeanneret |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 11
Issue 7
Pg. 1343-51
(Apr 03 2003)
ISSN: 0968-0896 [Print] England |
PMID | 12628660
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Dipeptides
- Peptides
- Photosensitizing Agents
- Protoporphyrins
- Aminolevulinic Acid
- protoporphyrin IX
- Peptide Hydrolases
- Neprilysin
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Topics |
- Aminolevulinic Acid
(analogs & derivatives, chemical synthesis, pharmacology)
- Cells, Cultured
- Dipeptides
(chemical synthesis, pharmacology)
- Endothelium, Vascular
(cytology, drug effects)
- Humans
- Hydrolysis
- Neprilysin
(metabolism)
- Peptide Hydrolases
(metabolism)
- Peptides
(chemical synthesis, pharmacology)
- Photochemotherapy
- Photosensitizing Agents
(chemical synthesis, pharmacology)
- Protoporphyrins
(metabolism)
- Spectrometry, Fluorescence
- Tumor Cells, Cultured
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