Prolidase, a Potential Enzyme Target for Melanoma: Design of Proline-Containing Dipeptide-like Prodrugs

The analyses indicated that prolidase might be a desirable enzyme target based on its differential expression in melanoma cancer cell lines and its high substrate specificity for dipeptides containing proline at the carboxy terminus. The results suggest the possibility of targeting prolidase with prodrugs of anticancer agents for enhanced selectivity. The feasibility of such a scenario was tested by synthesizing prodrugs of melphalan that comprised linkage of the carboxy terminus of the L-phenylalanine moiety of melphalan to the N-terminus of L and D stereoisomers of proline and determining their bioconversion and antiproliferative activities in SK-MEL-5 cells, a melanoma cancer cell line with high expression levels of prolidase.

Provided by: American Chemical Society Topic: Software Date Added: Jan 2005 Format: PDF

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