Improved synthesis and application of an alkyne-functionalized isoprenoid analogue to study the prenylomes of motor neurons, astrocytes and their stem cell progenitors

ABSTRACT: Protein prenylation is one example of a broad class of post-translational modifications where proteins are covalently linked to various hydrophobic moieties. To globally identify and monitor levels of all prenylated proteins in a cell simultaneously, our laboratory and others have developed chemical proteomic approaches that rely on the metabolic incorporation of isoprenoid analogues bearing bio-orthogonal functionality followed by enrichment and subsequent quantitative proteomic analysis. Here, we report on several improvements in the synthesis of the alkyne-containing isoprenoid analogue and the application of that probe study the prenylomes of motor neurons, astrocytes and their stem cell progenitors. The identification of numerous prenylated proteins in various ES-derived primary cells including 82 different proteins in ES astrocytes highlights the ability of this method to track the prenylation state of a diverse range of proteins. This strategy should be useful for clarifying how inhibitors of protein prenylation can serve as potent neurite-outgrowth-promoting agents.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Permanent Cell Line Cell, Dendritic Cell, Early Embryonic Cell, Embryonic Stem Cell

DISEASE(S): Amyotrophic Lateral Sclerosis

SUBMITTER: Shelby Auger  

LAB HEAD: Mark D Distefano

PROVIDER: PXD040354 | Pride | 2024-05-21

REPOSITORIES: Pride