DNA & protein binding miniature proteins
AssigneeYale University
InventorsAlanna Schepartz Shrader, Jason W.K. Chin, Reena Zutshi, Stacey E. Rutledge, Joanne D. Kehlbeck Martin, Neal J. Zondlo
Life of this patent
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Abstract
The present invention provides a protein scaffold, such as an avian pancreatic polypeptide, that can be modified by substitution of two or more amino acid residues that are exposed on the alpha helix domain of the polypeptide when the polypeptide is in a tertiary form.
Claims22
An avian pancreatic polypeptide modified by substitution of at least one amino acid residue, said at least one residue being exposed on the alpha helix domain of the polypeptide when the polypeptide is in a tertiary form.
A phage-display library comprising a plurality of recombinant phage that express a protein scaffold modified by substitution of at least one amino acid residue, said at least one residue being exposed on the polypeptide when the polypeptide is in a tertiary form.
An isolated polypeptide selected from the group consisting of:
- (a) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:
- 8, 9, 10, 11, 12, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 33, 34, 35, 36, 37, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 70, 71 or 72;
- (b) an isolated polypeptide comprising a fragment of at least twelve (12) amino acids of SEQ ID NO:
- 8, 9, 10, 11, 12, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 33, 34, 35, 36, 37, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 70, 71 or 72;
- (c) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:
- 8, 9, 10, 11, 12, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 33, 34, 35, 36, 37, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 70, 71 or 72;
- comprising one or more conservative amino acid substitutions;
- (d) an isolated polypeptide comprising the amino acid sequence of SEQ ID NO:
- 8, 9, 10, 11, 12, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 33, 34, 35, 36, 37, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 70, 71 or 72;
- comprising one or more naturally occurring amino acid sequence substitutions;
- and
- (e) an isolated polypeptide with at least ninety-five (95) percent amino acid homology to SEQ ID NO:
- 8, 9, 10, 11, 12, 13, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 33, 34, 35, 36, 37, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 70, 71 or 72.
A method of preparing a miniprotein that modulates the interaction between a known protein and another molecule, comprising the steps of:
- (a) identifying at least one amino acid residue contributes to the binding between a known protein and another molecule;
- and
- (b) modifying an avian pancreatic polypeptide by substitution of said at least one amino acid residue, such that it is exposed on the alpha helix domain of the polypeptide when the polypeptide is in a tertiary form.
Dependencies are inferred from the claim text.