A strategy for the generation of biomimetic ligands for affinity chromatography. Combinatorial synthesis and biological evaluation of an IgG binding ligand.
An IgG-binding ligand library comprising 88 adsorbents based on a known lead compound (Li et al., 1998) was generated on an agarose solid phase. Individual members of the library were synthesized in two chemical steps using cyanuric chloride as the scaffold immobilized on the beaded support. The library was screened for binding of pure human IgG, whence selected ligands from the library were further assessed for specificity by the purification of IgG from human plasma. The potential of this strategy for the rapid identification and evaluation of chemical leads was demonstrated by the discovery of ligands with IgG binding capabilities. It was found that ligands comprising 3-aminophenol and an aminonaphthol moiety substituted on a triazine nucleus generally performed better than other ligands in the library. An immobilized ligand 22/8 adsorbent was able to purify IgG with high yield and a purity >99% from diluted human plasma.
Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, UK.
S F
SF
Teng
K
K
Sproule
A
A
Hussain
C R
CR
Lowe
D000327:Adsorption; D000345:Affinity Labels / Q000737:chemistry* / Q000378:metabolism; D000588:Amines / Q000378:metabolism*; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification / Q000378:metabolism*; D008024:Ligands; D018716:Molecular Mimicry; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000345:Affinity Labels; D000588:Amines; D007074:Immunoglobulin G; D008024:Ligands