Ligand Engineering via Yeast Surface Display and Adherent Cell Panning

  • Lawrence A. Stern
  • Patrick S. Lown
  • Benjamin J. HackelEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2070)


High-throughput ligand discovery and evolution—via genotype-phenotype linkage strategies—empower molecularly targeted therapy, diagnostics, and fundamental science. Maintaining high-quality target antigen in these selections, particularly for membrane targets, is often a technical challenge. Panning yeast-displayed ligand libraries on intact mammalian cells expressing the molecular target has emerged as an effective strategy. Herein we describe the techniques used to select target-binding ligands via this approach including the use of target-negative cells to deplete non-specific binders and avidity reduction to preferentially select high-affinity ligands.

Key words

Avidity Cell panning Depletion Ligand Protein engineering Specificity Yeast surface display 



This chapter describes work funded by the American Cancer Society (130418-RSG-17-110-01-TBG to B.J.H.), the National Institutes of Health (R01 EB023339 to B.J.H.), and the California Tobacco-Related Disease Research Grants Program Office of the University of California (28FT-0072 to L.A.S.).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2020

Authors and Affiliations

  • Lawrence A. Stern
    • 1
  • Patrick S. Lown
    • 2
  • Benjamin J. Hackel
    • 2
    Email author
  1. 1.Department of Hematology and Hematopoietic Cell TransplantationBeckman Research Institute of the City of HopeDuarteUSA
  2. 2.Department of Chemical Engineering and Materials ScienceUniversity of Minnesota—Twin CitiesMinneapolisUSA

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