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Protein Engineering vol. 1 no. 6 pp. 493-498, 1987
© 1987 Oxford University Press

OTHER

Diphtheria toxin receptor binding domain substitution with interleukin-2: genetic construction and properties of a diphtheria toxin-related interleukin-2 fusion protein

D.P. Williams1,2, K. Parker3, P. Bacha3, W. Bishai1,4, M. Borowski1,*, F. Genbauffe1,3, T.B. Strom5 and J.R. Murphy1

1Evans Department of Clinical Research and Department of Medicine, University Hospital, Boston University Medical Center Boston, MA 02118 2Department of Microbiology, Boston University School of Medicine Boston, MA 02119 3Seragen, Inc. Hopkinton, MA 01748 4Department of Microbiology and Molecular Genetics, Harvard Medical School Boston, MA 02115 5Charles A.Dana Research Institute, Harvard Thorndike Laboratory, Beth Israel Hospital, Harvard Medical School Boston, MA 02215, USA

We have genetically replaced the diphtheria toxin receptor binding domain with a synthetic gene encoding interleukin-2 (IL-2) and a translational stop signal. The diphtheria toxin-related T-cell growth factor fusion gene encodes a 70 586-d polypeptide, pro-BL-2-toxin. The mature form of IL-2- toxin has a deduced mol. wt of 68 086 and is shown to be exported to the periplasmic compartment of Escherichia coli (pABI508), and contain immunologic determinants intrinsic to both its diphtheria toxin and IL-2 components. EL-2-toxin has been purified from periplasmic extracts of recombinant strains of E.coli (pABI508) by immunoaffinity chromatography using immobilized anti-IL-2. The purified chimeric toxin is shown to selectively inhibit protein synthesis in IL-2 receptor bearing targeted cells, whereas cell lines which do not express the IL-2 receptor are resistant to IL-2-toxin action.

Keywords: diphtheria toxin/interleukin-2


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