Multi-drug delivery system using streptavidin-transforming growth factor-alpha chimeric protein.
Tissue-specific delivery of a variety of molecules has been a valuable technique for biological and medical research. Therefore, we have constructed a recombinant plasmid containing the coding regions for streptavidin core and mature human transforming growth factor-alpha (TGF-alpha). The recombinant plasmid has been expressed in Escherichia coli to produce a chimeric protein with both streptavidin and TGF-alpha activity. The streptavidin-TGF-alpha chimeric protein (ST-TGF-alpha) could efficiently transfer biotinylated beta-galactosidase into A431 cells via the epidermal growth factor receptor. More than 99% of the cells contained the enzyme transferred. Furthermore, ST-TGF-alpha complexed with biotinylated-glucose oxidase had a significant cytotoxic effect when incubated with A431 cells. These findings suggest that the ST-TGF-alpha chimeric protein could be used to deliver proteins of interest into target cells without the need for chemical linkage or genetic construction. Essentially, ST-TGF-alpha serves as a high-modular "molecular bridge" for the passage of a wide variety of effector molecules into target cells.
Ohno
K
K
Department of Pathology, New York University Medical Center, New York, NY 10016, USA.
Meruelo
D
D
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001710:Biotin / Q000378:metabolism; D002294:Carcinoma, Squamous Cell; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005949:Glucose Oxidase / Q000633:toxicity; D006801:Humans; D008969:Molecular Sequence Data; D011869:Radioligand Assay; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000633:toxicity; D019809:Streptavidin; D016211:Transforming Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000378:metabolism
D001426:Bacterial Proteins; D004337:Drug Carriers; D011993:Recombinant Fusion Proteins; D016211:Transforming Growth Factor alpha; C101927:streptavidin-transforming growth factor-alpha protein, recombinant; D004815:Epidermal Growth Factor; D001710:Biotin; D019809:Streptavidin; D005949:Glucose Oxidase; D066246:ErbB Receptors; D001616:beta-Galactosidase