A synthetic Protein G adsorbent based on the multi-component Ugi reaction for the purification of mammalian immunoglobulins

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Jianing QianC R Lowe

Abstract

Numerous efforts have been devoted to develop synthetic affinity ligands mimicking natural immunoglobulin-binding proteins, such as Proteins A and L, in order to overcome intrinsic drawbacks involving their high cost and acidic pH elution. However, few reports have focused on a Protein G mimic. This work describes the use of the solid phase multi-component Ugi reaction to generate a low cost, rationally designed, affinity ligand to mimic Protein G for the purification of mammalian immunoglobulins, including the heavy-chain only camelid IgGs, with effective elution at neutral pH. An aldehyde-functionalised Sepharose™ resin constituted one component (aldehyde) of the four-component Ugi reaction, whilst the other three components (a primary or secondary amine, a carboxylic acid and an isonitrile) were varied to generate a tri-substituted Ugi scaffold, with a wide range of functionality, suitable for mimicking peptides for immunoglobulin purification. Ligand A2C11I1 was designed to mimic Asn35 and Trp43 of Protein G (PDB: 1FCC) and in silico docking into the Fc domain showed a key binding interface closely resembling native Protein G. This candidate ligand demonstrated affinity towards IgGs derived from human, cow, goat, mouse, she...Continue Reading

References

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Mar 3, 2005·Journal of Chromatography. a·A Cecília A RoqueChristopher R Lowe
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Citations

Apr 25, 2013·Biotechnology and Bioengineering·Graziella El KhouryChristopher R Lowe
Jan 10, 2016·Journal of Chromatography. a·Hong-Fei TongShan-Jing Yao
Dec 15, 2015·Journal of Molecular Recognition : JMR·Laura RoweChristopher R Lowe
Nov 10, 2012·Biotechnology Journal·Kristian KallbergLeif Bulow
Apr 5, 2016·Journal of Chromatography. a·Chen ChenChristopher R Lowe
Oct 1, 2015·Journal of Chromatography. a·Ana Sofia PinaA Cecília A Roque
Dec 18, 2013·Biotechnology Advances·Ana Sofia PinaAna Cecília A Roque
Jul 12, 2017·Bioconjugate Chemistry·Nika Kruljec, Tomaž Bratkovič
Jun 7, 2014·Chembiochem : a European Journal of Chemical Biology·Ana S PinaA Cecília A Roque
Jun 3, 2015·Journal of Separation Science·Gérald PerretEgisto Boschetti
Oct 1, 2014·Bioengineering·Petra GronemeyerJochen Strube
Sep 21, 2020·Journal of Separation Science·David SýkoraVladimír Král
Dec 17, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Hannah R ReeseStefano Menegatti
Feb 12, 2020·Journal of Chromatography. a·Manuel J B MatosA C A Roque
Aug 15, 2018·ACS Combinatorial Science·Ronak Afshari, Ahmad Shaabani

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