Back to Search
Start Over
Abnormal Cannabidiol Modulates Vitamin A Metabolism by Acting as a Competitive Inhibitor of CRBP1
- Source :
- ACS chemical biology. 14(3)
- Publication Year :
- 2019
-
Abstract
- Cellular retinol-binding proteins (CRBPs) facilitate the uptake and intracellular transport of vitamin A. They integrate retinoid metabolism, playing an important role in regulating the synthesis of bioactive vitamin A metabolites. Thus, CRBPs constitute potential pharmacological targets to modulate cellular retinoid status that in turn may have applications in the treatment of certain immunological, metabolic, and ocular disorders. Here we identify abnormal cannabidiol (abn-CBD) as a nonretinoid inhibitor of cellular retinol-binding protein 1 (CRBP1). X-ray crystal structures of CRBP1 in complex with abn-CBD and its derivatives revealed a distinctive mode of protein–ligand interaction and provided a molecular basis for the high affinity and selectivity of this compound. We demonstrated that abn-CBD modulates the flux of retinoids via the retinoid cycle in vivo. Furthermore, the biological activity of abn-CBD was evidenced by its ability to protect against light-induced retinal damage in Balb/cJ mice. Altogether, our findings indicate that targeting selected CRBPs with a small-molecule inhibitor can potentially lead to the development of new therapeutic agents to counteract diseases with etiologies involving imbalance in retinoid metabolism or signaling.
- Subjects :
- 0301 basic medicine
Vitamin
Light
medicine.drug_class
Drug Evaluation, Preclinical
Ligands
01 natural sciences
Biochemistry
Article
Cell Line
Small Molecule Libraries
03 medical and health sciences
chemistry.chemical_compound
Retinoids
Structure-Activity Relationship
Abnormal cannabidiol
Isomerism
In vivo
medicine
Animals
Humans
Retinoid
Amino Acid Sequence
Vitamin A
Mice, Inbred BALB C
010405 organic chemistry
Vitamin A metabolism
Retinal Degeneration
Biological activity
Biological Transport
Retinol-Binding Proteins, Cellular
General Medicine
Resorcinols
0104 chemical sciences
Cell biology
Kinetics
030104 developmental biology
chemistry
Molecular Medicine
Competitive inhibitor
Flux (metabolism)
Oxidation-Reduction
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 15548937
- Volume :
- 14
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- ACS chemical biology
- Accession number :
- edsair.doi.dedup.....aec4ee93906ec86a998d7837fc2dec8f