主权项 |
1. A polypeptide comprising a modified fibronectin type III (Fn3) domain, wherein the modified Fn3 domain comprises an amino acid sequence wherein the amino acid corresponding to residue 58 of SEQ ID NO: 1 is mutated, and wherein
the solubility of the modified Fn3 domain is enhanced relative to the solubility of a Fn3 domain wherein the amino acid corresponding to residue 58 of SEQ ID NO: 1 is not mutated, provided that in the modified Fn3 domain, the amino acid corresponding to residue 58 of SEQ ID NO: 1 is not mutated to Ala (A) or Ile (I); if the amino acid corresponding to residue 58 of SEQ ID NO: 1 is mutated to Ile (I), at least one of the amino acids corresponding to residues 23-29, 52-54 and 56 of SEQ ID NO:1 is the same as the corresponding residue of SEQ ID NO: 1; if the amino acid corresponding to residue 58 of SEQ ID NO: 1 is mutated to Ala (A), at least one of the amino acids corresponding to residues 23, 24, 26, 29, 52-54, and 56 of SEQ ID NO:1 is the same as the corresponding residue of SEQ ID NO: 1; or if the amino acid corresponding to residue 58 of SEQ ID NO: 1 is mutated to Ala (A), three residues of the BC loop are the same as the corresponding residues in the BC loop of SEQ ID NO:1, or two residues of the DE loop are the same as the corresponding residues in the DE loop of SEQ ID NO:1;
and wherein the modified Fn3 domain is selected from a 10Fn3 domain, a 10Fn3 domain, and a 14Fn3 domain. |