Selective toxicity of amino-terminal modified rnase a superfamily polypeptides
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsSusanna M. Rybak, Dianne L. Newton
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Abstract
This invention provides RNase A superfamily polypeptides with modified amino terminal which can be used to selectively kill target Kaposi's sarcoma cells, neoplastic endothelial cells, and non-neoplastic endothelial cells. In certain embodiments of the invention, the amino terminal modification consists of an addition of 4 amino acid sequence consisting of the SLHV sequence at position −4 to −1 to the eosinophil derived neurotoxin protein. The amino terminal addition is capable of directing the claimed RNase A superfamily polypeptides to proliferating endothelial cells, such as Kaposi's sarcoma cells, and selectively killing these cells.
Claims10
An isolated RNase A superfamily polypeptide having an N-terminus of the sequence:
- X1X2SLX3V (SEQ ID NO:9), wherein X1 represents methionine, X2 represents glycine, and X3 represents any amino acid residue, said RNase A superfamily polypeptide being selectively toxic to a proliferating endothelial cell and having at least 90% sequence identity to SEQ ID NO:4.
A pharmaceutical composition comprising
- a. a unit dosage RNase A superfamily polypeptide comprising an N-terminus of the sequence:
- X1X2SLX3V (SEQ ID NO:9), wherein X1 represents methionine, X2 represents glycine, and X3 represents any amino acid residue, said RNase A superfamily polypeptide being selectively toxic to a proliferating endothelial cell and having at least 90% sequence identity to SEQ ID NO:4;
- and
- b. a pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.