Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII

Morrill, P.R., Gupta, G., Sproule, K., Winzor, D. J., Christensen, J., Mollerup, I. and Lowe, C. R. (2002) Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 774 1: 1-15. doi:10.1016/S1570-0232(02)00103-4


Author Morrill, P.R.
Gupta, G.
Sproule, K.
Winzor, D. J.
Christensen, J.
Mollerup, I.
Lowe, C. R.
Title Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII
Journal name Journal of chromatography. B, Analytical technologies in the biomedical and life sciences   Check publisher's open access policy
ISSN 1570-0232
Publication date 2002-07-05
Year available 2002
Sub-type Article (original research)
DOI 10.1016/S1570-0232(02)00103-4
Volume 774
Issue 1
Start page 1
End page 15
Total pages 15
Place of publication Amsterdam
Publisher Elsevier Science
Collection year 2002
Language eng
Subject C1
270100 Biochemistry and Cell Biology
780105 Biological sciences
0699 Other Biological Sciences
Abstract The selection, synthesis and chromatographic evaluation of a synthetic affinity adsorbent for human recombinant factor VIIa is described. The requirement for a metal ion-dependent immunoadsorbent step in the purification of the recombinant human clotting factor, FVIIa, has been obviated by using the X-ray crystallographic structure of the complex of tissue factor (TF) and Factor VIIa and has directed our combinatorial approach to select, synthesise and evaluate a rationally-selected affinity adsorbent from a limited library of putative ligands. The selected and optimised ligand comprises a triazine scaffold bis-substituted with 3-aminobenzoic acid and has been shown to bind selectively to FVIIa in a Ca2+-dependent manner. The adsorbent purifies FVIIa to almost identical purity (>99%), yield (99%), activation/degradation profile and impurity content (∼1000 ppm) as the current immunoadsorption process, while displaying a 10-fold higher static capacity and substantially higher reusability and durability. © 2002 Elsevier Science B.V. All rights reserved.
Keyword Affinity ligands
Combinatorial chemistry
Immunoadsorbent
Recombinant human clotting factor VII
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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Created: Wed, 15 Aug 2007, 03:38:27 EST