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

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. A laminin fragment peptide, Ac-AASIKVAVSADR-NH2 (5), and its derivativ...

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Bibliographic Details
Published inAnticancer research Vol. 20; no. 3A; p. 1381
Main Authors Yamazaki, Y, Tsuruga, M, Gentsch, B, Oka, S, Kleinman, H K, Mokotoff, M
Format Journal Article
LanguageEnglish
Published Greece 01.05.2000
Subjects
Adhesiveness
Antineoplastic Agents - administration & dosage
Biotransformation
Drug Carriers
Drug Delivery Systems
Endopeptidases - metabolism
Humans
Laminin - metabolism
Peptides - administration & dosage
Peptides - chemistry
Tumor Cells, Cultured
U937 Cells
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Summary: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. 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. 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. 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.
ISSN:0250-7005