Peptoid ligands that bind selectively to phosphoproteins

Di Cai, A. Young Lee, Cheng Ming Chiang, Thomas Kodadek

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Synthetic equivalents of phosphoprotein-specific antibodies would be valuable reagents for biological research, since these antibodies can often be difficult to produce. Protein phosphorylation is thought to result in significant conformational changes in most substrate proteins. Therefore, one approach might be to simply screen combinatorial libraries for ligands to the phosphorylated state in the hope of isolating a ligand that binds to a pocket created by the conformational shift. In this study, we probe this strategy by screening a peptoid library for ligands to the phosphorylated form of the Brd4 chromatin adaptor and transcriptional coactivator protein. We find that peptoids with high selectivity for binding to the phosphorylation form of Brd4 can indeed be isolated in this screen. Moreover, these ligands do not bind promiscuously to other phospho-proteins. However, attempts to employ these reagents as antibody substitutes in an immunoaffinity purification-like application showed that they do not perform as well as bona fide antibodies and that significant optimization will be required. This study highlights the potential and current limitations of a naïve library screening strategy for phosphoprotein-specific antibody surrogates.

Original languageEnglish (US)
Pages (from-to)4960-4964
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume21
Issue number17
DOIs
StatePublished - Sep 1 2011

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Peptoids
Phosphoproteins
Ligands
Antibodies
Phosphorylation
Screening
Proteins
Chromatin
Purification
Substrates
Research

Keywords

  • Combinatorial chemistry
  • Peptoid
  • Phosphorylation
  • Screening

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Peptoid ligands that bind selectively to phosphoproteins. / Cai, Di; Lee, A. Young; Chiang, Cheng Ming; Kodadek, Thomas.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 21, No. 17, 01.09.2011, p. 4960-4964.

Research output: Contribution to journalArticle

Cai, Di ; Lee, A. Young ; Chiang, Cheng Ming ; Kodadek, Thomas. / Peptoid ligands that bind selectively to phosphoproteins. In: Bioorganic and Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 17. pp. 4960-4964.
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