Oxidation-resistant ribonuclease inhibitor
First Claim
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1. An oxidation-resistant engineered ribonuclease inhibitor (RI) selected from the group consisting of:
- (i) a RI comprising the reference sequence of SEQ ID NO;
3, except for an alanine substitution of at least one cysteine residue at positions 95, 96, 329 and 330; and
(ii) a RI comprising the reference sequence of SEQ ID NO;
2, except for an alanine substitution of at least one cysteine residue at positions 324 and 325,the RI having a greater resistance to oxidation relative to the reference sequence for the RI and retaining its specificity and binding affinity to ribonuclease.
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Abstract
Mutant forms of ribonuclease inhibitor are described which are rendered more resistant to oxidation while retaining affinity for both ribonuclease and angiogenin. The mutant forms have another amino acid, typically an alanine, substituted for one or more of the adjacent cysteine residues in the wild-type sequence to prevent the formation of unwanted disulfide bonds which can disrupt the effectiveness of the molecule.
18 Citations
11 Claims
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1. An oxidation-resistant engineered ribonuclease inhibitor (RI) selected from the group consisting of:
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(i) a RI comprising the reference sequence of SEQ ID NO;
3, except for an alanine substitution of at least one cysteine residue at positions 95, 96, 329 and 330; and(ii) a RI comprising the reference sequence of SEQ ID NO;
2, except for an alanine substitution of at least one cysteine residue at positions 324 and 325,the RI having a greater resistance to oxidation relative to the reference sequence for the RI and retaining its specificity and binding affinity to ribonuclease. - View Dependent Claims (2, 3, 4)
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5. An oxidation-resistant ribonuclease inhibitor (RI) comprising the reference sequence of SEQ ID NO:
- 3, except for an alanine residue at one or more of positions 95, 96, 329 and 330.
- View Dependent Claims (6, 7, 10, 11)
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8. An oxidation-resistant ribonuclease inhibitor (RI) comprising the reference sequence of SEQ ID NO:
- 2, except for an alanine residue at one or both of positions 324 and 325.
- View Dependent Claims (9)
Specification