Relaxin analogs
View Patent ↗Human relaxin analogs, polypeptide compositions related thereto, as well as nucleotide compositions encoding the same, are provided.
1. A purified polypeptide analog of a mammalian relaxin 2 (RLN2) protein comprising an amino acid substitution to an amino acid other than the wild-type at residue 23 in the A chain, wherein the analog has increased selectivity for activation of the relaxin receptor LGR7 relative to the wild-type protein.
2. The polypeptide analog of claim 1 , wherein the amino acid at residue 23 is selected from alanine, glycine, serine, threonine, isoleucine and leucine.
3. The polypeptide analog of claim 1 , wherein the analog has enhanced biological activity relative to the wild-type protein.
4. The polypeptide analog according to claim 1 , wherein the polypeptide analog is covalently linked to a RLN2 B chain.
5. The polypeptide analog of claim 4 , wherein the RLN2 B chain has a wild-type amino acid sequence.
6. The polypeptide analog of claim 4 , wherein the RLN2 B chain is a variant of the wild-type RLN2 B chain amino acid sequence.
7. The polypeptide analog according to claim 4 , wherein the A chain and the B chain are covalently linked to a relaxin C chain.
8. The polypeptide analog of claim 7 , wherein the C chain is a truncated C chain.
9. A pharmaceutical formulation comprising a polypeptide analog according to claim 1 ; and a pharmaceutically acceptable excipient.
10. A purified polypeptide analog of a mammalian relaxin 2 (RLN2) protein comprising an amino acid substitution at one or both of amino acid residues 16 and 17 to an amino acid other than the wild-type in the A chain, wherein the analog has increased activity for activation of the relaxin receptors LGR7 or LGR8 relative to the wild type protein.
11. The polypeptide analog of claim 10 , wherein the polypeptide is a human RLN2 polypeptide comprising a substitution at residue 16 to an amino acid other than threonine.
12. The polypeptide analog of claim 10 , wherein the polypeptide is a human RLN2 polypeptide comprising a substitution at residue 17 to an amino acid other than lysine.
13. The polypeptide analog of claim 11 , wherein the amino acid at residue 16 or 17 is selected from alanine, glycine, isoleucine and leucine.
14. A purified polypeptide analog of a human relaxin 2 (RLN2) protein comprising:
an amino acid substitution at residue 23 in the A chain of a mammalian RLN2 protein to alanine, glycine, serine, threonine, isoleucine or leucine; and
an amino acid substitution at one or both residues 16 and 17 in the A chain of said mammalian RLN2 protein to alanine, glycine, isoleucine or leucine;
wherein the analog has increased selectivity for the relaxin receptor LGR7 and enhanced biological activity relative to the wild-type protein.
15. The polypeptide analog according to claim 14 , wherein the polypeptide analog is covalently linked to a RLN2 B chain.
16. The polypeptide analog of claim 15 , wherein the RLN2 B chain has a wild-type amino acid sequence.
17. The polypeptide analog of claim 15 , wherein the RLN2 B chain is a variant of the wild-type RLN2 B chain amino acid sequence.
18. The polypeptide analog according to claim 15 , wherein the A chain and the B chain are covalently linked to a relaxin C chain.
19. The polypeptide analog of claim 18 , wherein the C chain is a truncated C chain.
20. A pharmaceutical formulation comprising a polypeptide analog according to claim 14 ; and a pharmaceutically acceptable excipient.