# A NOVEL CHEMOPROTEOMIC TECHNOLOGY TO REVEAL GLOBAL SMALL MOLECULE-PROTEOME-WIDE INTERACTIONS IN LIVE CELLS.

> **NIH NIH R21** · PELIAN BIOSCIENCES, LLC · 2020 · $177,725

## Abstract

Project Summary/Abstract
Small molecules are abundant in nature, where they perform various roles in living cells, as enzyme cofactors,
signaling molecules in biological networks or as metabolic components. As a consequence of physical
interaction with proteins, they may illicit profound changes in protein function that can have physiological
outcomes. Several biophysical and biochemical approaches, including high-throughput screening strategies,
have been developed in an effort to globally or individually detect protein-metabolite interactions in vitro, in situ
or in vivo. The use of affinity tags and protein overexpression has enabled the detection of metabolome-wide
small molecule ligands of each protein target in turn. However, these methods are compounded by a necessity
to isolate the protein target of interest from the cell, thus providing lesser physiological relevance and
complicating downstream validation and analysis. Excluding the use of protein or small molecule arrays, the
remaining in situ or in vivo approaches are limited to permit the identification of proteome-wide targets of each
small molecule in turn. These technological restrictions translate to a bottleneck in data acquisition and
difficulties in validation when determining important functional roles of small molecules in the context of
biological networks. Therefore, currently, there are no technologies to globally identify the proteome-wide
targets of all small molecules in live cells without isolation and disturbance of the intact targets within the
intracellular milieu. We aim to overcome this limitation by developing a new chemoproteomic technology that
will permit direct isolation and characterization by mass spectrometry of metabolome-wide small molecules
with their respective proteome-wide targets in situ in a single experiment. This truly global approach will deliver
a powerful new tool for the investigator of protein-small molecule interactions by enabling the acquisition of the
complete protein-metabolite interactome in live cells. We expect that the information gathered by adopting this
technology will yield novel insights in small molecule-protein regulation, providing more comprehensive and
larger biological networks for the analysis of signaling pathways of physiological relevance, and facilitating
comparisons of entire organism protein-small molecule interactions under different experimental conditions in a
similar manner to other current –omics disciplines.

## Key facts

- **NIH application ID:** 9858373
- **Project number:** 5R21GM126264-03
- **Recipient organization:** PELIAN BIOSCIENCES, LLC
- **Principal Investigator:** Michael Marco Bruno
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,725
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858373

## Citation

> US National Institutes of Health, RePORTER application 9858373, A NOVEL CHEMOPROTEOMIC TECHNOLOGY TO REVEAL GLOBAL SMALL MOLECULE-PROTEOME-WIDE INTERACTIONS IN LIVE CELLS. (5R21GM126264-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9858373. Licensed CC0.

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