New developments in affinity chromatography with potential application in the production of biopharmaceuticals.
Affinity chromatography is likely to play an increasingly important role in the purification of pharmaceutical proteins. This review describes new approaches to the design and synthesis of affinity ligands based on the ability to combine knowledge of X-ray crystallographic or NMR structures with defined or combinatorial chemical synthesis. The de novo design process is based on peptidal templates, complementarity to surface exposed residues and mimicking natural biological recognition. Examples of ligands designed to bind specifically to kallikrein, elastase, immunoglobulin G, insulin, alpha(1)-antitrypsin, clotting factor VII and glyco-proteins are given. The exceptional selectivity and stability of these synthetic ligands allows their use in harsh manufacturing environments.
Lowe
C R
CR
Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK. crl1@biotech.cam.ac.il
Lowe
A R
AR
Gupta
G
G
D001702:Biopharmaceutics / Q000379:methods*; D002846:Chromatography, Affinity / Q000379:methods* / Q000639:trends; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy
D008024:Ligands