Fenretinide binding to the lysosomal protein saposin D alters ceramide solubilization and hydrolysis†,10.1039/D0MD00182A

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Fenretinide binding to the lysosomal protein saposin D alters ceramide solubilization and hydrolysis†

Brandon T. Milliken,Lindy Melegari,Gideon L. Smith,Kris Grohn,Fadi Bou-Abdallah

RSC Medicinal Chemistry Pub Date : 07/14/2020 00:00:00 , DOI:10.1039/D0MD00182A

Abstract

Fenretinide is a synthetic retinoid pharmaceutical linked to ceramide build-up in vivo. Saposin D is an intralysosomal protein necessary for ceramide binding/degradation. We show, via electronic absorption spectroscopy, fluorescence spectroscopy, and ceramide hydrolysis assays, that fenretinide is bound by saposin D {K_a = (1.45 ± 0.49) × 10⁵ M⁻¹}, and affects ceramide solubilization/degradation.