Macrocyclic polypeptides

Abstract

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.