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  Rescue of glycosylphosphatidylinositol-anchored protein biosynthesis using synthetic glycosylphosphatidylinositol oligosaccharides

Guerrero, P. A., Murakami, Y., Malik, A., Seeberger, P. H., Kinoshita, T., & Varón Silva, D. (2021). Rescue of glycosylphosphatidylinositol-anchored protein biosynthesis using synthetic glycosylphosphatidylinositol oligosaccharides. ACS Chemical Biology, 16(11), 2297-2306. doi:10.1021/acschembio.1c00465.

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 Creators:
Guerrero, Paula A.1, Author           
Murakami, Yoshiko, Author
Malik, Ankita1, Author           
Seeberger, Peter H.2, Author           
Kinoshita, Taroh, Author
Varón Silva, Daniel1, Author           
Affiliations:
1Daniel Varón Silva, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863302              
2Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863308              

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Free keywords: Glycosylphosphatidylinositol, glycolipids, GPI-anchored proteins, biosynthesis rescue, GPI deficiencies.
 Abstract: The attachment of proteins to the cell membrane using a glycosylphosphatidylinositol (GPI) anchor is a ubiquitous process in eukaryotic cells. Deficiencies in the biosynthesis of GPIs and the concomitant production of GPI-anchored proteins lead to a series of rare and complicated disorders associated with inherited GPI deficiencies (IGDs) in humans. Currently, there is no treatment for patients suffering from IGDs. Here, we report the design, synthesis and use of GPI fragments to rescue the biosynthesis of GPI-anchored proteins caused by mutation in genes involved in the assembly of GPI-glycolipids in cells. We demonstrated that the synthetic fragments GlcNAc-PI (1), Man-GlcN-PI (5), and GlcN-PI with two (3) and three lipid chains (4) rescue the deletion of the GPI biosynthesis in cells devoid of the PIGA, PIGL, and PIGW genes in vitro. The compounds allowed for concentration-dependent recovery of GPI biosynthesis and were highly active on the cytoplasmic face of the ER membrane. These synthetic molecules are leads for the development of treatments for IGDs and tools to study GPI-APs biosynthesis.

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Language(s): eng - English
 Dates: 2021-09-222021-10-072021
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1021/acschembio.1c00465
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Title: ACS Chemical Biology
  Abbreviation : ACS Chem. Biol.
Source Genre: Journal
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Publ. Info: Washington, D.C. : American Chemical Society
Pages: - Volume / Issue: 16 (11) Sequence Number: - Start / End Page: 2297 - 2306 Identifier: ISSN: 1554-8929