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The large-scale interactions between bile acids and proteins

ABSTRACT: Characterization of small-molecule and protein interactions is essential for elucidating protein biochemical activity, regulatory mechanisms, and the intricate relationships within biological signaling pathways. A variety of methodologies have been developed to identify interactions between proteins and small molecules. Small-molecule probe-based pull-down assays represent a well-established and intuitive approach for identifying proteins that interact with specific small molecules. However, large-scale probe synthesis remains challenging due to its complex procedures and labor-intensive nature, thereby hindering the comprehensive mapping of small-molecule-protein interaction networks. In this study, we introduce a strategy employing solid-phase assisted probe synthesis and 96-well based target capture. This approach capitalizes on the immobilization of small molecules on a solid support, enabling efficient and high-throughput synthesis of diverse probes. Applying this method, we synthesized 13 chemically cleavable bile acid probes and identified a total of 7,306 interaction pairs between 13 bile acids and 1883 proteins. This large dataset provides a wealth of information about the interactions of bile acids with cellular proteins. Furthermore, we conducted a comparative analysis between SD (standard diet) and HFM (high-fat diet-induced obesity model) groups. This analysis led to the identification of 2,639 differential bile acid-protein pairs, highlighting the changes in these interactions in response to dietary fat intake. These results demonstrate the potential of our method to reveal novel insights into the complex interplay between small molecules and proteins in different biological contexts.

ORGANISM(S): Mus Musculus

SUBMITTER: Jinlong Wang

PROVIDER: PXD072384 | iProX | Wed Dec 24 00:00:00 GMT 2025

REPOSITORIES: iProX

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