Cytotoxic ribonuclease variants
AssigneeWisconsin Alumni Research Foundation
InventorsRonald T. Raines, George N. Phillips, Jr., R. Jeremy Johnson, Jason G. McCoy
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Abstract
Cytotoxic variants of human ribonuclease 1 (RNase 1) identified through analysis of the interaction between RNase 1 and the human ribonuclease inhibitor (hRI) as defined by the three dimensional (3-D) atomic structure of the RNase1 hRI complex are disclosed. Also disclosed is the 3-D structure of the hRI·RNase 1 complex and methods for designing the RNase 1 variants.
Claims9
An engineered human Ribonuclease (RNase 1) polypeptide only differing in amino acid sequence from an RNase 1 protein comprising SEQ ID NO:2 by at least four amino acid substitutions, the at least four amino acid substitutions consisting of:
- (a) at least one amino acid substitution located within residues 85 to 94 of SEQ ID NO:2;
- (b) the amino acid substitution G38R of SEQ ID NO:2;
- and
- (c) at least two amino acid substitutions at amino acid residues selected from the group consisting of residues 4, 7, 11, 31, 32, 39, 41, 42, 66, 67, 71, 111 and 118 of SEQ ID NO:2.
Dependencies are inferred from the claim text.