Trifunctional fatty acid derivatives: the impact of diazirine placement

  • Chem Commun (Camb). 2024 Jun 25;60(52):6651-6654. doi: 10.1039/d4cc00974f.
Scotland E Farley  1  2 ,  Ryu Hashimoto  1  3 ,  Judah Evangelista  1  2 ,  Frank Stein  4 ,  Per Haberkant  4 ,  Kazuya Kikuchi  3 ,  Fikadu G Tafesse  2 ,  Carsten Schultz  1
Affiliations
  • 1. Oregon Health & Science University, Department of Chemical Physiology and Biochemistry, USA. [email protected].
  • 2. Oregon Health & Science University, Department of Molecular Microbiology and Immunology, Portland, OR, 97239, USA. [email protected].
  • 3. Osaka University, Department of Applied Chemistry, Graduate School of Engineering, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.
  • 4. European Molecular Biology Laboratory, Proteomics Core Facility, 69117, Heidelberg, Germany.
PMID: 38856656 DOI: 10.1039/d4cc00974f
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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