Synthetic isohirudins with improved stability

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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530326, 530416, 530418, 536 235, 4353201, 435 691, C07K 710, A61K 3764

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active

052867145

ABSTRACT:
The invention relates to novel synthetic isohirudins which have improved stability owing to exchange in the region of the Asp-Gly motif. This results, on the one hand, in an increase in the yield during workup and, on the other hand, in making possible pharmaceutical formulation as directly injectable solution ready for use.

REFERENCES:
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patent: 4791100 (1988-12-01), Kramer et al.
patent: 5095092 (1992-03-01), Badziong et al.
Harvey et al., "Cloning & Expression of a cDNA Coding for the Anti-Coagulant Hirudin from the Blood Sucking Leech, Hirudo Medicinalis," PNAS 83: 1084-1088 (1986).
Baskova et al., "Hirudin from Leech Heads and Whole Leeches and Pseudo-Hirudin from Leech Bodies," Thrombosis Research 30:459-467 (1983).
Bowie et al., "Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions," Science 247 1306-1310 (1990).
Smith et al., Principles of Biochemistry: General Aspects, 7th Ed., pp. 32-33, pp. 814-815.
Dodt et al., "Interaction of Site Specific Hirudin Variants with .delta.-thrombin," FEBS Letters, vol. 229 (1): 87-90 (1988).
Dodt et al., "The Complete Amino Acid Sequence of Hirudin, a Thrombin Specific Inhibitor. Application of Colour Carboxymethylations", FEBS Letters, vol. 164 (2): pp. 180-184 (1984).
Geiger et al., "Deamidation, Isomerization, and Racemization at Asparaginyl and Aspartyl Residues in Peptides," The Journal of Biological Chemistry, vol. 262, No. 2, 1987, pp. 785-794.
Stephenson et al., "Succinimide Formation from Aspartyl and Asparaginyl Peptides as a Model for the Spontaneous Degradation of Proteins," The Journal of Biological Chemistry, vol. 264, No. 11, 1989, pp. 6164-6170.

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