DNA-Encoded Combinatorial Library of Macrocyclic Peptoids

Min Hyeon Shin, Kang Ju Lee, Hyun Suk Lim

Research output: Contribution to journalArticle

Abstract

We report the design and synthesis of a DNA-encoded one-bead one-compound library of cyclic peptoids composed of more than 11 million molecules. We show that affinity-based screening of this large library can identify cyclic peptoid ligands for a target protein. In this work, we developed a simple method for amplifying the PCR product from DNA tags on a single bead, thereby enabling determination of the structures of hit cyclic peptoids with no need for high-throughput sequencing and complicated data analysis. We also developed a sublibrary screening strategy to minimize false positives caused by the interference of coding DNA tags before starting laborious and impractical hit confirmation. Given the simplicity and robustness of the synthesis and screening, along with the desirable features of macrocyclic peptoids including improved conformational rigidity, our method will be highly useful for discovering biologically active molecules modulating challenging targets such as protein-protein interactions that are not easily targeted by typical peptidomimetics and small-molecules.

Original languageEnglish (US)
JournalBioconjugate Chemistry
DOIs
StateAccepted/In press - Jan 1 2019
Externally publishedYes

Fingerprint

Peptoids
DNA
Screening
Proteins
Molecules
Peptidomimetics
Rigidity
Libraries
Ligands
Throughput
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

DNA-Encoded Combinatorial Library of Macrocyclic Peptoids. / Shin, Min Hyeon; Lee, Kang Ju; Lim, Hyun Suk.

In: Bioconjugate Chemistry, 01.01.2019.

Research output: Contribution to journalArticle

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