Bioadhesive peptides as potential anticancer drug carriers: activation via isopeptide deblocking by proteases.

Background: Bioadhesive peptides are potentially useful as anticancer drug carriers, if the bioadhesivity becomes active only at the tumor site. We propose that this function can be achieved by the prodrug strategy using proteases in tumors.

Materials And Methods: A laminin fragment peptide, Ac-AASIKVAVSADR-NH2 (5), and its derivatives, Ac-AASIK(L) VAVSADR-NH2 (6), Ac-AASIDpm(NH2)VAVSADR-NH2 (7) and Ac-AASIDpm(L)(NH2)VAVSADR-NH2 (8), were synthesized and tested for their bioadhesive activity with 6 cancer cell lines.

Results: The strength of the binding was in the order of 5 >> 7 > or = 8 > or = 6. The attachment of mouse whole blood cells to peptide 6-coated surface was also weaker than to 5-coated surface. The Leu isopeptide linkage in 6 was enzymatically cleaved by the cells.

Conclusion: The present results suggest that isopeptide 6, working as a prodrug form for the bioadhesive peptide 5, could serve as an anticancer drug carrier for tumor targeting.