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

Brandon T. Milliken; Lindy Melegari; Gideon L. Smith; Kris Grohn; Aaron J. Wolfe; Kelsey Moody; Fadi Bou-Abdallah; Robert P. Doyle

doi:10.1039/d0md00182a

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

Brandon T. Milliken, Lindy Melegari, Gideon L. Smith, Kris Grohn, Aaron J. Wolfe, Kelsey Moody, Fadi Bou-Abdallah, Robert P. Doyle

Research output: Contribution to journal › Article › peer-review

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 {Ka = (1.45 ± 0.49) × 105 M-1}, and affects ceramide solubilization/degradation.

Original language	English (US)
Pages (from-to)	1048-1052
Number of pages	5
Journal	RSC Medicinal Chemistry
Volume	11
Issue number	9
DOIs	https://doi.org/10.1039/d0md00182a
State	Published - Sep 2020

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Organic Chemistry

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title = "Fenretinide binding to the lysosomal protein saposin D alters ceramide solubilization and hydrolysis",

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 {Ka = (1.45 ± 0.49) × 105 M-1}, and affects ceramide solubilization/degradation.",

author = "Milliken, {Brandon T.} and Lindy Melegari and Smith, {Gideon L.} and Kris Grohn and Wolfe, {Aaron J.} and Kelsey Moody and Fadi Bou-Abdallah and Doyle, {Robert P.}",

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T1 - Fenretinide binding to the lysosomal protein saposin D alters ceramide solubilization and hydrolysis

AU - Milliken, Brandon T.

AU - Melegari, Lindy

AU - Smith, Gideon L.

AU - Grohn, Kris

AU - Wolfe, Aaron J.

AU - Moody, Kelsey

AU - Bou-Abdallah, Fadi

AU - Doyle, Robert P.

PY - 2020/9

Y1 - 2020/9

N2 - 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 {Ka = (1.45 ± 0.49) × 105 M-1}, and affects ceramide solubilization/degradation.

AB - 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 {Ka = (1.45 ± 0.49) × 105 M-1}, and affects ceramide solubilization/degradation.

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EP - 1052

JO - RSC Medicinal Chemistry

JF - RSC Medicinal Chemistry

IS - 9

ER -

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

Abstract

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