Unveiling the molecular dynamics of a nitrile-containing 5-lipoxygenase-activating protein antagonist in primary macrophages through Raman spectroscopy
Chemical Science, cilt.17, sa.3, ss.1613-1623, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 17 Sayı: 3
- 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
- Sayfa Sayıları: ss.1613-1623
- 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.