Downregulation of circulating ghrelin and therapeutic applications thereof
AssigneeUniversity of Kentucky Research Foundation
InventorsChang-Guo Zhan, Fang Zheng
Life of this patent
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Abstract
Compositions and methods for converting ghrelin to desacyl-ghrelin include a butyrylcholinesterase (BChE) polypeptide variant. The presently-disclosed subject matter includes compositions and methods for use in directly downregulating ghrelin. In particular, certain embodiments relate to compositions and methods for hydrolyzing/deacylating ghrelin to desacyl-ghrelin and applications thereof in the treatment of disorders involving ghrelin.
Claims20
A method of inactivating ghrelin, comprising administering a ghrelin hydrolase to convert the ghrelin to desacyl-ghrelin, wherein the ghrelin hydrolase comprises a butyrylcholinesterase (BChE) polypeptide variant comprising an amino acid sequence having 1, 2, 3, 4, 5, or 6 mutations relative to the amino acid sequence of SEQ ID NO:
- 2, said mutations selected from the group consisting of A199S, F227A, T284S, P285I or P285A or P285Q or P285S, S287G, V288I, A328W, Y332G, and F398I, and wherein the amino acid sequence of the BChE polypeptide variant is optionally truncated relative to the amino acid sequence of SEQ ID NO:
- 2, such that one or more residues from 1 to 67 and/or one or more residues from 443 to 574 is truncated.
A butyrylcholinesterase (BChE) polypeptide variant comprising an amino acid sequence having 1, 2, 3, or 4 mutations relative to the amino acid sequence of SEQ ID NO:
- 2, said mutations selected from the group consisting of T284S, P285I, V288I, F398I;
- and wherein the amino acid sequence of the BChE polypeptide variant is optionally truncated relative to the amino acid sequence of SEQ ID NO:
- 2, such that one or more residues from 1 to 67 and/or one or more residues from 443 to 574 is truncated.
A method of inactivating ghrelin in a subject in need of treatment for a substance use disorder, comprising administering to the subject a composition comprising a butyrylcholinesterase (BChE) or BChE polypeptide variant, and a pharmaceutically acceptable carrier, wherein the BChE polypeptide variant comprises an amino acid sequence having 1, 2, 3, 4, 5, or 6 mutations relative to the amino acid sequence of SEQ ID NO:
- 2, said mutations selected from the group consisting of A199S, F227A, T284S, P285I or P285A or P285Q or P285S, S287G, V288I, A328W, Y332G, and F398I, and wherein the amino acid sequence of the BChE polypeptide variant is optionally truncated relative to the amino acid sequence of SEQ ID NO:
- 2, such that one or more residues from 1 to 67 and/or one or more residues from 443 to 574 is truncated.
21-30. (canceled)
Dependencies are inferred from the claim text.