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Reproducible Discovery of Cell-Binding Peptides “Lost” in Bulk Amplification via Emulsion Amplification in Phage Display Panning

Wadim L. Matochko, Frédérique Deiss, Yang Yang, View ORCID ProfileRatmir Derda
doi: https://doi.org/10.1101/2021.10.31.466683
Wadim L. Matochko
Department of Chemistry, University of Alberta, Edmonton Alberta T6G 2G2 (Canada)
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Frédérique Deiss
Department of Chemistry, University of Alberta, Edmonton Alberta T6G 2G2 (Canada)
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Yang Yang
Department of Chemistry, University of Alberta, Edmonton Alberta T6G 2G2 (Canada)
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Ratmir Derda
Department of Chemistry, University of Alberta, Edmonton Alberta T6G 2G2 (Canada)
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  • ORCID record for Ratmir Derda
  • For correspondence: ratmir@ualberta.ca
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Abstract

Many pharmaceutically-relevant cell surface receptors are functional only in the context of intact cells. Phage display, while being a powerful method for the discovery of ligands for purified proteins often fails to identify a diverse set of ligands to receptors on a cell membrane mosaic. To understand this deficiency, we examined growth bias in naïve phage display libraries and observed that it fundamentally changes selection outcomes: The presence of growth-biased (parasite) phage clones in a phage library is detrimental to selection and cell-based panning of such biased libraries is poised to yield ligands from within a small parasite population. Importantly, amplification of phage libraries in water-oil emulsions suppressed the amplification of parasites and steered the selection of biased phage libraries away from parasite population. Attenuation of the growth bias through the use of emulsion amplification reproducibly discovers the ligands for cell-surface receptors that cannot be identified in screen that use conventional ‘bulk’ amplification.

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Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 03, 2021.
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Reproducible Discovery of Cell-Binding Peptides “Lost” in Bulk Amplification via Emulsion Amplification in Phage Display Panning
Wadim L. Matochko, Frédérique Deiss, Yang Yang, Ratmir Derda
bioRxiv 2021.10.31.466683; doi: https://doi.org/10.1101/2021.10.31.466683
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Reproducible Discovery of Cell-Binding Peptides “Lost” in Bulk Amplification via Emulsion Amplification in Phage Display Panning
Wadim L. Matochko, Frédérique Deiss, Yang Yang, Ratmir Derda
bioRxiv 2021.10.31.466683; doi: https://doi.org/10.1101/2021.10.31.466683

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