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Design, synthesis, and application of a Protein A mimetic

Nature Biotechnology volume 16, pages 190–195 (1998)Cite this article

Abstract

Low-molecular-weight synthetic molecules that mimic the activity of native biological macromolecules have therapeutic potential, utility in large-scale production of biopharmaceuticals, and the capacity to act as probes to study molecular recognition events. We have developed a nonpeptidyl mimic for Staphylococcus aureus Protein A (SpA). The specific recognition and complexation elements between the B domain (Fb) of SpA and the Fc fragment of IgG were identified from the x-ray crystallographic structure. Computer-aided molecular modeling was used to design a series of biomimetic molecules around the Phe132-Tyr133 dipeptide involved in its binding to IgG. One of the ligands binds IgG competitively with SpA in solution and when immobilized on agarose beads, with an affinity constant of 105-106 M−1. The immobilized artificial Protein A was used to purify IgG from human plasma and murine IgG from ascites fluid, and to remove bovine IgG from fetal calf serum.

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Author information

Author notes

  1. David J. Stewart

    Present address: Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, NY, 11724

  2. Rongxiu Li

    Present address: Shangai Research Centre of Biotechnology, 500 Caobao Rd., Shanghai, 200233, P.R. China

Authors and Affiliations

  1. Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QT, UK

    Rongxiu Li, David J. Stewart & Christopher R. Lowe

  2. Affinity Chromatography Ltd., 307 Huntingdon Rd., Girton, Cambridge, CB3 OJX, UK

    Victor Dowd & Stephen J. Burton

Authors
  1. Rongxiu Li
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  2. Victor Dowd
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  5. Christopher R. Lowe
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Corresponding author

Correspondence to Christopher R. Lowe.

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Li, R., Dowd, V., Stewart, D. et al. Design, synthesis, and application of a Protein A mimetic. Nat Biotechnol 16, 190–195 (1998). https://doi.org/10.1038/nbt0298-190

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