Design and synthesis of a DNA-encoded combinatorial library of bicyclic peptoids. (15th October 2021)

• Record Type: Journal Article
• Authors: Lee, Kang Ju; Bang, Geul; Kim, Yong Wook; Shin, Min Hyeon; Lim, Hyun-Suk
• Is Part Of: Bioorganic & medicinal chemistry. Volume 48(2021)
• Publication Date: 2021-10-15
• Subjects: DNA-encoded chemical library -- Bicyclic peptoids -- Peptidomimetics; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2021.116423
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Here we describe the design and synthesis of a DNA-encoded library of bicyclic peptoids. We show that our solid-phase strategy is facile and DNA-compatible, yielding a structurally diverse combinatorial library of bicyclic peptoids of various ring sizes. We also demonstrate that affinity-based screening of a DNA-encoded library of bicyclic peptoids enables to efficiently identify high-affinity ligands for a target protein. Given their highly constraint structures, as well as increased cell permeability and proteolytic stability relative to native peptides, bicyclic peptoids could be an excellent source of protein capture agents. As such, our DNA-encoded library of bicyclic peptoids will serve as versatile tools that facilitate the generation of potent ligands against many challenging targets, such as intracellular protein–protein interactions.