"A 27-Amino-Acid Synthetic Peptide Corresponding to the NH2-Terminal Zinc-Binding Domain of Endostatin Is Responsible for Its Antitumor Activity Robert M. Tjin Tham Sjin1, Ronit Satchi-Fainaro1, Amy E. Birsner1, V.M. Sadagopa Ramanujam2, Judah Folkman1 and Kashi Javaherian1 1 Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts and 2 Division of Human Nutrition, Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas
Requests for reprints: Kashi Javaherian, Vascular Biology Program, Department of Surgery, Children's Hospital Boston, Karp Family Research Laboratories, Room 11.213, One Blackfan Circle, Boston, MA 02115. Phone: 617-919-2392; Fax: 617-739-5891; E-mail: kashi.javaherian@childrens.harvard.edu.
The first recombinant endostatin that elicited strong antitumor activity was expressed in Escherichia coli and administered as a suspension. Under these conditions, the protein retained its full antiangiogenic activity. Lack of requirement for a folded structure prompted us to investigate antitumor properties of synthetic peptides corresponding to different regions of endostatin. Here, we show that the entire antitumor, antimigration, and antipermeability activities of endostatin are mimicked by a 27-amino-acid peptide corresponding to the NH2-terminal domain of endostatin. This peptide contains three histidines that are responsible for zinc binding. Mutations of the zinc-binding histidines abolished its antitumor and antimigration activities, but not antipermeability properties."
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