Growth hormone antagonists
AssigneeOhio University
InventorsJohn J. Kopchick, Wen Y. Chen
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Abstract
The present invention relates to antagonists of vertebrate growth hormones obtained by mutation of the third alpha helix of such proteins (especially bovine or human GHs). These mutants have growth inhibitory or other GH-antagonizing effects. These novel hormones may be administered exogenously to animals, or transgenic animals may be made that express the antagonist. Animals have been made which exhibited a reduced growth phenotype.
Claims27
A vertebrate growth hormone in which the amino acid position in said vertebrate growth hormone corresponding to amino acid Gly 119 of bovine growth hormone is deleted or substituted with an amino acid, said vertebrate growth hormone having growth hormone antagonist activity.
A vertebrate growth hormone in which there are two substitutions or deletions at amino acid positions corresponding to the amino acid positions of bovine growth hormone, said substitutions or deletions at Gly 119 and at an amino acid position selected from the group consisting of Ala 122, Leu 123, Ile 120, Leu 116, Asp 115 and Glu 118, said vertebrate growth hormone having growth hormone antagonist activity.
Human growth hormone in which amino acid Gly 120 is deleted or substituted with an amino acid, said human growth hormone having growth hormone antagonist activity.
Human growth hormone wherein the amino acid position corresponding to amino acid Glu 117 of bovine growth hormone is substituted with Leu, the amino acid position corresponding to amino acid Gly 119 of bovine growth hormone is substituted with Arg and the amino acid position corresponding to amino acid Ala 122 of bovine growth hormone is substituted with Asp, said human growth hormone having growth hormone antagonist activity.
Human growth hormone in which there are two substitutions or deletions at amino acid positions corresponding to the amino acid positions of bovine growth hormone, said substitutions or deletions at Gly 119 and at an amino acid position selected from the group consisting of Ala 122, Leu 123, Ile 120, Leu 116, Asp 115 and Glu 118, said human growth hormone having growth hormone antagonist activity.
Human growth hormone wherein the amino acid position corresponding to amino acid Glu 111 of bovine growth hormone is substituted with Leu, the amino acid position corresponding to amino acid Gly 119 of bovine growth hormone is substituted with Trp and amino acid position corresponding to amino acid Arg 125 of bovine growth hormone is substituted with Leu, said human growth hormone having growth hormone antagonist activity.
Bovine growth hormone in which amino acid Gly 119 is deleted or substituted with an amino acid, said bovine growth hormone having growth hormone antagonist activity.
Bovine growth hormone wherein amino acid Glu 117 is substituted with Leu, amino acid Gly 119 is substituted with Arg and amino acid Ala 122 is substituted with Asp, said bovine growth hormone having growth hormone antagonist activity.
Bovine growth hormone in which there are two substitutions or deletions, said substitutions or deletions at amino acid position Gly 119 and at an amino acid position selected from the group consisting of Ala 122, Leu 123, Ile 120, Leu 116, Asp 115 and Glu 118, said bovine growth hormone having growth hormone antagonist activity.
Bovine growth hormone wherein amino acid Glu 111 is substituted with Leu, amino acid Gly 119 is substituted with Trp and amino acid Arg 125 is substituted with Leu, said bovine growth hormone having growth hormone antagonist activity.
Dependencies are inferred from the claim text.