Mutations in the gene encoding the alpha chain of platelet glyco

Details Mutations in the gene encoding the alpha chain of platelet glyco Mutations in the gene encoding the alpha chain of platelet glyco

1993-10-14

1997-01-14

Patterson, Jr., Charles L.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

530380, 530395, 424 9463, 424 9464, 128899, C07K 14705, C07K 14745, A61K 3817, A61K 3836

Patent

active

055939597

ABSTRACT:
The subject invention provides purified polypeptides encoded by naturally-occurring wild-type platelet glycoprotein Ib alpha having a mutation which renders the polypeptide more reactive with von Willebrand factor. Preferably, the mutation is in the hinge region of GP Ib.alpha., such as the substitution of valine for glycine at residue 233. These mutations alter the three-dimensional structure of the mutant polypeptide from a beta bend conformation to an alpha helix formation, and also create an amphipathic region within the mutant polypeptide. DNA encoding the mutant polypeptides, as well as expression systems for the production of the mutant polypeptides, are also provided. Methods and compositions using the mutant polypeptides and DNA oligomers complementary to the mutant polypeptides are further provided.

REFERENCES:
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V. A. Canfield et al. "Isolation and Characterization of the .alpha. and .beta.. . . " Biochem. Biophys. Res. Commun. 147(2)526-534 (Sep. 1987).
J. L. Miller et al. "von Willebrand Factor Binds to Platelets . . . " J. Clin. Invest. 72:1532-1542 (Nov. 1983).
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James Chen, et al., "Comparative X-ray Crystallographic Evidence for a .beta.-Bend Conformation as the Active Structure for Peptide T in T4 Receptor Recognition", Journal of Protein Chemistry, 8: 87-100 (1989).
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Dipak Shah, et al., "Correlation of .beta.-bend conformations of tetrapeptides with their activities in CD4-receptor binding assays", Int. J. Peptide Protein Res. 34: 325-332 (1989).
James M. Chen, et al., "Comparison of the Predicted Structure for the Activated Form of the P21 Protein with the X-ray Crystal Structure", Journal of Protein Chemistry 9: 543-547 (1990).

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