Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer

Sooho Ko, Joo Young Kim, Jung Yeon Park, You Jin Jung, Min Jae Choi, Kyeong Sik Jin, Yongju Kim, Yong Beom Lim, Woo Jin Jeong

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

This study presents the development of a β-hairpin (tryptophan zipper, Trpzip)-based molecular tweezer (MT) that can control the folding and binding of α-helical peptides. When an α-helix isolated from the p53 protein was conjugated with Trpzip in an optimized macrocyclic structure, the folded β-hairpin stabilized the helix conformation through the side chain-to-side chain stapling strategy, which notably enhanced target (hDM2) affinity of the peptide. On the other hand, the helicity and binding affinity were significantly reduced when the hairpin was unfolded by a redox stimulus. This stimulus-responsive property was translated into the effective capture and release of model multivalent biomaterials, hDM2-gold nanoparticle conjugates. Since numerous protein interactions are mediated by α-helical peptides, these results suggest that the β-hairpin-based MT holds great potential to be utilized in various biomedical applications, such as protein interaction inhibition and cancer biomarker (e.g., circulating tumor cells and exosomes) detection.

Original languageEnglish
Pages (from-to)9600-9607
Number of pages8
JournalChemical Science
Volume14
Issue number35
DOIs
Publication statusPublished - 2023 Sept 1

Bibliographical note

Publisher Copyright:
© 2023 The Royal Society of Chemistry.

ASJC Scopus subject areas

  • General Chemistry

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