title: Enhancement of the cancer targeting specificity of buforin IIb by fusion with an anionic peptide via a matrix metalloproteinases-cleavable linker.
abstract: Buforin IIb is a novel cell-penetrating anticancer peptide derived from histone H2A. In this study, we enhanced the cancer targeting specificity of buforin IIb using a tumor-associated enzyme-controlled activation strategy. Buforin IIb was fused with an anionic peptide (modified magainin intervening sequence, MMIS), which neutralizes the positive charge of buforin IIb and thus renders it inactive, via a matrix metalloproteinases (MMPs)-cleavable linker. The resulting MMIS:buforin IIb fusion peptide was completely inactive against MMPs-nonproducing cells. However, when the fusion peptide was administrated to MMPs-producing cancer cells, it regained the killing activity by releasing free buforin IIb through MMPs-mediated cleavage. Moreover, the activity of the fusion peptide toward MMPs-producing cancer cells was significantly decreased when the cells were pretreated with a MMP inhibitor. Taken together, these data indicate that the cancer targeting specificity of MMIS:buforin IIb is enhanced compared to the parent peptide by reactivation at the specialized areas where MMPs are pathologically produced.
authors.affiliation: Department of Biology, Research Institute of Life Science, Gyeongsang National University, 900 Gajwa-dong, Jinju 660-701, Republic of Korea.
authors.forename: Ju Hye
authors.initials: JH
authors.lastname: Jang
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sun Chang
authors.initials: SC
authors.lastname: Kim
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Cho
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011506:Proteins / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D010455:Peptides; D011506:Proteins; C097849:buforin II; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9