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[Preprint]. 2024 May 15:2024.05.15.594383. [Version 1] doi: 10.1101/2024.05.15.594383

Trifunctional fatty acid derivatives demonstrate the impact of diazirine placement

Scotland E Farley, Ryu Hashimoto, Judah Evangelista, Frank Stein, Per Haberkant, Kazuya Kikuchi, Fikadu G Tafesse, Carsten Schultz
PMCID: PMC11118520  PMID: 38798378

ABSTRACT

Functionalized lipid probes are a critical new tool to interrogate the function of individual lipid species, but the structural parameters that constrain their utility have not been thoroughly described. Here, we synthesize three palmitic acid derivatives with a diazirine at different positions on the acyl chain and examine their metabolism, subcellular localization, and protein interactions. We demonstrate that while they produce very similar metabolites and subcellular distributions, probes with the diazirine at either end pulldown distinct subsets of proteins after photo-crosslinking. This highlights the importance of thoughtful diazirine placement when developing probes based on biological molecules.

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