Development of a Peptidomimetic Ligand for Efficient Isolation and Purification of Factor VIII via Affinity Chromatography
| Autor: | Alexey V. Khrenov, Evgueni L. Saenko, Burkhardt Laufer, Sebastian Knör, Charlotte A. E. Hauser, Horst Kessler |
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| Rok vydání: | 2007 |
| Předmět: |
Serum
Severe bleeding congenital hereditary and neonatal diseases and abnormalities Polymers Peptidomimetic Peptide Tripeptide Ligands Chromatography Affinity chemistry.chemical_compound Drug Stability Affinity chromatography hemic and lymphatic diseases Drug Discovery Peptide synthesis Humans chemistry.chemical_classification Factor VIII Chromatography Indoleacetic Acids Elution Ligand Molecular Mimicry Stereoisomerism Recombinant Proteins Amino Acid Substitution chemistry Molecular Medicine Oligopeptides Peptide Hydrolases Protein Binding |
| Zdroj: | Journal of Medicinal Chemistry. 50:4329-4339 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm070304x |
| Popis: | Hemophilia A, one of the most severe bleeding disorders, results from an inherited deficiency of factor VIII (FVIII) function. Treatment by injection of FVIII has been a common procedure for decades. Nevertheless, the production and purification of FVIII remains a challenging task. Current procedures using immunoaffinity chromatography are expensive and suffer from the instability of the applied antibody ligands, which elute along with the product and contaminate it. Recently, FVIII was purified by use of octapeptide ligands, but their low protease-resistance limits their application. We here report the systematic rational and combinatorial optimization procedure that allowed us to transfer the octapeptide ligands into a small peptidomimetic. This compound is the smallest ligand known for separation of such a large protein (330 kDa). It not only binds and purifies FVIII with high efficiency but also is stable, protease-resistant, and cheap to produce in preparative scale. Hence it offers a valuable alternative to antibody-based purification procedures. |
| Databáze: | OpenAIRE |
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