Proteome-wide target profiling of a-helix mimetics
File(s)
Published online version
Author(s)
Type
Journal Article
Abstract
The dysregulation of protein–protein interactions (PPIs) in disease states is well established, yet they are challenging to target, owing to the large surface area and featureless nature of protein binding interfaces. For targeting helix-mediated interactions, α-helix mimetics present a promising strategy. These are versatile small molecule scaffolds, capable of mimicking the hotspot residues on an α-helix. A wide range of such scaffolds have been reported, yet their target protein selectivity in the context of a whole proteome requires further exploration. Here, we report the affinity-based protein profiling of three structurally distinct classes of α-helix mimetics, N-substituted oligobenzamides, pyrrolopyrimidines, and oxopiperazines. This represents the first direct cross-comparison of different helix mimetic scaffolds, revealing significant differences in proteome-wide selectivity.
Date Issued
2026-07-21
Date Acceptance
2026-07-16
Citation
RSC Chemical Biology, 2026
ISSN
2633-0679
Publisher
The Royal Society of Chemistry
Journal / Book Title
RSC Chemical Biology
Copyright Statement
© 2026 The Author(s). Published by the Royal Society of Chemistry This article is licensed under a Creative Commons Attribution 4.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.
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Publication Status
Published online
Date Publish Online
2026-07-21