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Synthesis of a (13)C-methylene-labeled isoleucine precursor as a useful tool for studying protein side-chain interactions and dynamics.

PubMed

Authors: Höfurthner T, Toscano G, Kontaxis G, Beier A, Mayer M, Geist L, McConnell DB, Weinstabl H, Lichtenecker R, Konrat R

Year

2024

Paper ID

9444

Status

Peer-reviewed

Abstract Read

~2 min

Abstract Words

105

Citations

N/A

Abstract

In this study, we present the synthesis and incorporation of a metabolic isoleucine precursor compound for selective methylene labeling. The utility of this novel α-ketoacid isotopologue is shown by incorporation into the protein Brd4-BD1, which regulates gene expression by binding to acetylated histones. High quality single quantum C- H-HSQC were obtained, as well as triple quantum HTQC spectra, which are superior in terms of significantly increased C-T times. Additionally, large chemical shift perturbations upon ligand binding were observed. Our study thus proves the great sensitivity of this precursor as a reporter for side-chain dynamic studies and for investigations of CH-π interactions in protein-ligand complexes.

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In this study, we present the synthesis and incorporation of a metabolic isoleucine precursor compound for selective methylene labeling.

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References & Citation Signals

[1] DOI https://doi.org/10.1007/s10858-023-00427-2 [2] Publisher https://pubmed.ncbi.nlm.nih.gov/37816933/

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