Unveiling the molecular dynamics of a nitrile-containing 5-lipoxygenase-activating protein antagonist in primary macrophages through Raman spectroscopy


Schultz C., Jordan P. M., Dahlke P., GÜR MAZ Z. T., BANOĞLU E., Meyer-Zedler T., ...Daha Fazla

Chemical Science, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1039/d5sc09493c
  • Dergi Adı: Chemical Science
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chimica, Compendex, Directory of Open Access Journals, Nature Index
  • Gazi Üniversitesi Adresli: Evet

Özet

The nitrile (–C 00000000000000000 00000000000000000 00000000000000000 01111111111111110 00000000000000000 01111111111111110 00000000000000000 01111111111111110 00000000000000000 00000000000000000 00000000000000000 N) functional group is a versatile pharmacophore motif that also serves as an intrinsic, bioorthogonal Raman tag in the silent wavenumber region (1800–2700 cm−1). Here, we exploit this dual functionality to track the potent nitrile-containing 5-lipoxygenase-activating protein (FLAP) antagonist BRP-685 in primary human macrophages using label-free spontaneous and stimulated Raman scattering. This approach enables direct intracellular localization at biologically relevant, low micromolar concentrations without chemical modification or external labels. Quantitative Raman imaging reveals that BRP-685 preferentially accumulates in lipid droplets, distinct from its membrane-bound target site at the nuclear envelope/endoplasmic reticulum. Multiplexed analysis with an alkyne-tagged lipid analog uncovers a unique distribution pattern, suggesting that lipid droplets act as intracellular reservoirs for highly lipophilic drugs.