Reagents and methods for controlling protein function and interaction
OwnerDavid BAKER, Daniel CUNNINGHAM-BRYANT +7inventors
InventorsDavid BAKER, Daniel CUNNINGHAM-BRYANT, Emily DIETER, Glenna FOIGHT, Per GREISEN, Dustin MALY, Keunwan PARK, Zhizhi WANG, Cindy WEI
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Abstract
The present disclosure provides danoprevir/NS3a complex reader (DNCR) and grazoprevir/NS3a complex readers (GNCR) polypeptides, fusion proteins, and combinations and their use.
Claims57
A non-naturally occurring polypeptide comprising the general formula X1-X2-X3-X4-X5, wherein:
- X1 optionally comprises first, second, third, and fourth helical domains;
- X2 comprises a fifth helical domain comprising the amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the full length of HSIVYAIEAAIF (SEQ ID NO:1), wherein 1, 2, 3, or all 4 of the following changes from SEQ ID NO:1 are not permissible:
- H1K, S2L, Y5E, and F12R
- X3 comprises a sixth helical domain;
- X4 comprises a seventh helical domain comprising the amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the full length of RNVEHALMRIVLAIY (SEQ ID NO:2), wherein 1, 2, 3, or all 4 of the following changes from SEQ ID NO:2 are not permissible:
- R1E, H5E, M8K, and L12K;
- and
- X5 comprises an eighth helical domain.
A non-naturally occurring polypeptide comprising the general formula X1-X2-X3-X4-X5-X6-X7, wherein:
- X1 comprises first helical domain;
- X2 comprises a second helical domain comprising the amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the full length of
- (SEQ ID NO:
- 20)
- DLANLAVAAVLTACL,
- wherein 1, 2, 3, 4, 5, 6, or all 7 of the following changes from SEQ ID NO:20 are not permissible:
- D1K, N4S, L5Q, A8E, L11K, T12L, and L15E;
- X3 comprises a third helical domain;
- X4 comprises a fourth helical domain comprising the amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the full length of RAVILAIM (SEQ ID NO:21), wherein 1, 2, 3, or all 4 of the following changes from SEQ ID NO:21 are not permissible:
- R1E, I4K, I7C, and M8E;
- X5 comprises a fifth helical domain;
- X6 comprises a sixth helical domain comprising the amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the full length of RAIWLAAE (SEQ ID NO:22), wherein 1, 2, 3, or all 4 of the following changes from SEQ ID NO:22 are not permissible:
- R1L, I3C, W4E, and A7Q;
- and
- X7 comprises seventh and eighth helical domains.
A polypeptide comprising the amino acid sequence selected from the group consisting SEQ ID NO:31-38, wherein the bolded amino acid residue is the catalytic position, wherein the bolded “S” residue represents catalytically active NS3a peptides, and wherein the bolded ‘S” residue can be substituted with an alanine (or other) residue to render the NS3a peptide catalytically dead.
Use of the polypeptide, fusion protein, recombinant fusion protein, combination, nucleic acid, expression vector, or host cell or any embodiment disclosed herein to carry out any methods, including but not limited to those disclosed herein.
Dependencies are inferred from the claim text.