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Title: Integration of phage and yeast display platforms: A reliable and cost effective approach for binning of peptides as displayed on-phage

Journal Article · · PLoS ONE
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [2];  [3];  [3]; ORCiD logo [4];  [4];  [5]; ORCiD logo [1]
  1. Eli Lilly Biotechnology Center, San Diego, CA (United States)
  2. Eli Lilly and Company, San Diego, CA (United States)
  3. Eli Lilly and Company, Indianapolis, IN (United States)
  4. Centro de Investigacion Lilly, Alcobenidas (Spain)
  5. Lilly Research Laboratories, Indianapolis, IN (United States)
+ Show Author Affiliations

Hundreds of target specific peptides are routinely discovered by peptide display platforms. However, due to the high cost of peptide synthesis only a limited number of peptides are chemically made for further analysis. Here we describe an accurate and cost effective method to bin peptides on-phage based on binding region(s), without any requirement for peptide or protein synthesis. This approach, which integrates phage and yeast display platforms, requires display of target and its alanine variants on yeast. Flow cytometry was used to detect binding of peptides on-phage to the target on yeast. Once hits were identified, they were synthesized to confirm their binding region(s) by HDX (Hydrogen deuterium exchange) and crystallography. Moreover, we have successfully shown that this approach can be implemented as part of a panning process to deplete non-functional peptides. This technique can be applied to any target that can be successfully displayed on yeast; it narrows down the number of peptides requiring synthesis; and its utilization during selection results in enrichment of peptide population against defined binding regions on the target.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1632885
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 6 Vol. 15; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Is Phage Display Technology on Target for Developing Peptide-Based Cancer Drugs? journal June 2004

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