Preprint Concept Paper Version 1 Preserved in Portico This version is not peer-reviewed

Bringing Functional Context to Emerging Proximity-Mapping Proteomics Tools

Version 1 : Received: 24 May 2022 / Approved: 30 May 2022 / Online: 30 May 2022 (06:13:07 CEST)

How to cite: Aye, Y. Bringing Functional Context to Emerging Proximity-Mapping Proteomics Tools. Preprints 2022, 2022050388. https://doi.org/10.20944/preprints202205.0388.v1 Aye, Y. Bringing Functional Context to Emerging Proximity-Mapping Proteomics Tools. Preprints 2022, 2022050388. https://doi.org/10.20944/preprints202205.0388.v1

Abstract

If one considers chemical-biology toolsets that have had the greatest impact on numerous fields of life sciences over the most recent years, proximity-labeling tools, such as APEX, and Bio-ID arguably lead the way. This article reflects upon the current state-of-the-art and discusses key limitations underlying these emerging approaches, in particular, the limited functional knowledge they provide in understanding local proteomes / interactomes. This limitation is directly linked to the use of non-biologically- or non-pharmaceutically-relevant reactive intermediates in the course of covalently labeling the local proteomes. As such, these methods cannot report on specific functions of localized protein players, nor can they scrutinize whether the specific functions of such proteins/interactomes can be directly manipulated by pharmacologically-relevant small-molecule ligands. The latest data hint that precision localized electrophile delivery concept ushers a means to address this limitation with high spatiotemporal resolution, and ultimately, in relevant live animals.

Keywords

proximity labeling; spatial omics; functional proteomics; interactome mapping; electrophile signaling

Subject

Chemistry and Materials Science, Medicinal Chemistry

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