MACROCYCLIC POLYPEPTIDES
Disclosed herein are macrocyclic polypeptides having no more than 3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID NO: 1-2.37 or a mirror image thereof, wherein the polypeptide includes both L and D amino acids, libraries of such polypeptides, and uses thereof.
1 . A macrocyclic polypeptide comprising or consisting of a polypeptide having no more than 3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID NO: 1-237 or a mirror image thereof, wherein the polypeptide includes both L and D amino acids.
2 . The polypeptide of claim 1 , wherein the polypeptide has at least one proline residue.
3 . The polypeptide of claim 1 , wherein the polypeptide is between 7 and 14 amino acid residues in length, or between 7 and 10 amino acid residues in length.
4 . The polypeptide of claim 2 , wherein each amino acid substitution occurs at a non-proline position.
5 . The polypeptide of claim 1 , wherein the amino acid substitutions do not include any non-proline residues being substituted with proline.
6 . The polypeptide of claim 1 , wherein each amino acid substitution maintains the chirality of the amino acid replaced.
7 . The polypeptide of claim 1 , wherein each amino acid substitution is an alpha amino acid.
8 . The polypeptide of claim 1 , wherein the polypeptide has at least 2, 3, 4, 5, 6, 7, 8, or more D amino acid residues.
9 . The polypeptide of claim 1 , wherein the polypeptide has no more than 2 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID NO: 1-237 or a mirror image thereof.
10 . The polypeptide of claim 1 , wherein the polypeptide has no more than 1 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID NO: 1-237 or a mirror image thereof.
11 . The polypeptide of claim 1 , comprising or consisting the amino acid sequence of any one of SEQ ID NO: 1-237 or a mirror image thereof.
12 . A polypeptide library, comprising two or more polypeptides having no more than 3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID NO: 1-237 or a mirror image thereof, wherein the polypeptide includes both L and D amino acids.
13 . The polypeptide library of claim 13 , comprising ten or more polypeptides having no more than 3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID NO: 1-237 or a mirror image thereof, wherein the polypeptide includes both L and D amino acids.
14 . The polypeptide library of claim 13 , comprising fifty or more polypeptides having no more than 3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID NO: 1-237 or a mirror image thereof, wherein the polypeptide includes both L and D amino acids.
15 . The polypeptide library of claim 14 , comprising two hundred or more polypeptides having no more than 3 amino acid substitutions compared to the amino acid sequence of any one of SEQ ID NO: 1-237 or a mirror image thereof, wherein the polypeptide includes both L and D amino acids.
16 . Use of the polypeptide of claim 1 as a scaffold for target-based drug design or to screen molecules of interest for binding to one or more of the polypeptides.