Synthesis and screening of bead-displayed combinatorial libraries

Todd M. Doran; Paige Dickson; John Maina Ndungu; Peng Ge; Irena Suponitsky-Kroyter; Hongchan An; Thomas Kodadek

doi:10.1016/bs.mie.2019.02.005

Synthesis and screening of bead-displayed combinatorial libraries

Todd M. Doran, Paige Dickson, John Maina Ndungu, Peng Ge, Irena Suponitsky-Kroyter, Hongchan An, Thomas Kodadek

Medicinal Chemistry

Research output: Chapter in Book/Report/Conference proceeding › Chapter

8 Scopus citations

Abstract

The development of faster and less expensive methods to discover bioactive small molecules remains a high priority in chemical biology. This article discusses one alternative to traditional high-throughput screening: the synthesis and screening of one bead one compound (OBOC) libraries. Protocols are provided to create and screen libraries of peptoid displayed on TentaGel beads, which is a cheap and relatively straightforward process for the identification of selective protein ligands. However, peptoids bind to proteins with modest affinity in most cases. Therefore, we also describe protocols to create libraries of stiffer oligomers called PICCOs (peptoid-inspired, conformationally constrained oligomers) that have proven to be a superior source of high affinity ligands.

Original language	English (US)
Title of host publication	Chemical and Synthetic Biology Approaches To Understand Cellular Functions - Part B
Editors	Arun K. Shukla
Publisher	Academic Press Inc.
Pages	91-127
Number of pages	37
ISBN (Print)	9780128181195
DOIs	https://doi.org/10.1016/bs.mie.2019.02.005
State	Published - 2019

Publication series

Name	Methods in Enzymology
Volume	622
ISSN (Print)	0076-6879
ISSN (Electronic)	1557-7988

Bibliographical note

Funding Information:
The National Institutes of Health (AG 054892) supported some of the work described here.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

High-throughput screening
One bead one compound libraries
Peptoid
Solid-phase synthesis

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10.1016/bs.mie.2019.02.005

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Doran, T. M., Dickson, P., Ndungu, J. M., Ge, P., Suponitsky-Kroyter, I., An, H., & Kodadek, T. (2019). Synthesis and screening of bead-displayed combinatorial libraries. In A. K. Shukla (Ed.), Chemical and Synthetic Biology Approaches To Understand Cellular Functions - Part B (pp. 91-127). (Methods in Enzymology; Vol. 622). Academic Press Inc.. https://doi.org/10.1016/bs.mie.2019.02.005

Synthesis and screening of bead-displayed combinatorial libraries. / Doran, Todd M.; Dickson, Paige; Ndungu, John Maina et al.
Chemical and Synthetic Biology Approaches To Understand Cellular Functions - Part B. ed. / Arun K. Shukla. Academic Press Inc., 2019. p. 91-127 (Methods in Enzymology; Vol. 622).

Research output: Chapter in Book/Report/Conference proceeding › Chapter

Doran, TM, Dickson, P, Ndungu, JM, Ge, P, Suponitsky-Kroyter, I, An, H & Kodadek, T 2019, Synthesis and screening of bead-displayed combinatorial libraries. in AK Shukla (ed.), Chemical and Synthetic Biology Approaches To Understand Cellular Functions - Part B. Methods in Enzymology, vol. 622, Academic Press Inc., pp. 91-127. https://doi.org/10.1016/bs.mie.2019.02.005

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Synthesis and screening of bead-displayed combinatorial libraries

Abstract

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Bibliographical note

Keywords

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