Development of a peptidomimetic ligand for efficient isolation and purification of factor VIII via affinity chromatography

Sebastian Knör, Alexey V. Khrenov, Burkhardt Laufer, Evgueni L. Saenko, Charlotte Hauser, Horst Kessler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4329-4339
Number of pages11
JournalJournal of Medicinal Chemistry
Volume50
Issue number18
DOIs
StatePublished - Sep 6 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Development of a peptidomimetic ligand for efficient isolation and purification of factor VIII via affinity chromatography'. Together they form a unique fingerprint.

Cite this