Novel prodrug approach to photodynamic therapy: Fmoc solid-phase synthesis of a cell permeable peptide incorporating 5-aminolaevulinic acid.
The first example of the synthesis of a peptide incorporating 5-aminolaevulinic acid (5-ALA) using standard Fmoc solid-phase chemistry is reported. The synthesised peptide contains residues 52-58 of the cell-permeable peptide Penetratin and represents a prototype for the enhanced topical delivery of 5-ALA using such oligopeptide vectors. Effective intracellular conversion of the peptide to the endogenous photosensitiser, protoporphyrin IX, is observed in PAM212 cells, thus demonstrating the potential of this approach for the development of novel peptide prodrugs for use in photodynamic therapy.
Dixon
Mark J
MJ
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Bourré
Ludovic
L
MacRobert
Alexander J
AJ
Eggleston
Ian M
IM
D000622:Aminolevulinic Acid / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015394:Molecular Structure; D010455:Peptides; D010539:Permeability; D010778:Photochemotherapy / Q000379:methods*; D011355:Prodrugs; D011524:Protoporphyrins / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors
D010455:Peptides; D011355:Prodrugs; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX