Synthesis of glycosylphosphatidylinositol (GPI)-anchor glycolipids bearing unsaturated lipids

Lee, B.-Y.; Seeberger, Peter H.; Silva, Daniel Varón

doi:10.1039/c5cc07694c

Cited by 18 publications

(15 citation statements)

References 26 publications

(29 reference statements)

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“…Fragments 1 , 2 , and 4 having saturated alkyl chains were accessible from the benzyl protected pseudodisaccharide 5 [15] . Fragment 3 , containing an unsaturated chain, required the use of the 2‐naphthylmethyl (Nap) protected pseudodisaccharide 6 [16] and H‐phosphonate 8 (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

“…The desired glycolipid 3 was accessible by treatment of 23 with anhydrous trifluoroacetic acid and anisole. [16] To study the biophysical properties of glycolipids, we analyzed monolayers of these compounds at the water-air interface by GIXD and IRRAS. [24] GIXD analysis showed pronounced effects due to the N-acetylglucosamine deacetylation and hence the loss of the zwitterionic character of the glycolipid.…”

Section: Discussionmentioning

confidence: 99%

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Zwitterionic Character and Lipid Composition Determine the Behaviour of Glycosylphosphatidylinositol Fragments in Monolayers

et al. 2021

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Glycosylphosphatidylinositols (GPIs) are complex glycolipids found in free form or anchoring proteins to the outer leaflet of the cell membrane in eukaryotes. GPIs have been associated with the formation of lipid rafts and protein sorting on membranes. The presence of a conserved glycan core with cellspecific modifications together with lipid remodelling during biosynthesis suggest that the properties of the glycolipids are being fine-tuned. We synthesized a series of GPI fragments and evaluated the interactions and arrangement of these glycolipids in monolayers as a 2-D membrane model. GIXD and IRRAS analyses showed the need of N-acetylglucosamine deacetylation for the formation of hydrogen bonds to obtain highly structured domains in the monolayers and an effect of the unsaturated lipids in formation and localization of the glycolipids within or between membrane microdomains. These results contribute to understand the role of these glycolipids and their modifications in the organization of membranes.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Zwitterionic Character and Lipid Composition Determine the Behaviour of Glycosylphosphatidylinositol Fragments in Monolayers

et al. 2021

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“…Recently, we demonstrated the utility of Nap‐protection for the synthesis of GPI derivatives and highlighted its advantages over benzyl ethers in the synthesis of challenging targets. Notably, this switch in protecting group does not affect the reactivity of the building blocks but gives good selectivity and glycosylation yields in the formation of 1,2‐ cis products …”

Section: Resultsmentioning

confidence: 99%

Synthesis of Galactosylated Glycosylphosphatidylinositol Derivatives from Trypanosoma brucei

Grube

Lee

Michel

et al. 2018

Chemistry A European J

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Trypanosoma brucei uses variant surface glycoproteins (VSGs) to evade the host immune system and ensure parasitic longevity in animals and humans. VSGs are attached to the cell membrane by complex glycosylphosphatidylinositol anchors (GPI). Distinguishing structural feature of VSG GPIs are multiple α- and β-galactosides attached to the conserved GPI core structure. T. brucei GPIs have been associated with macrophage activation and alleviation of parasitemia during infection, acting as disease onset delaying antigens. Literature reports that link structural modifications in the GPIs to changes in biological activity are contradictory. We have established a synthetic route to prepare structurally overlapping GPI derivatives bearing different T. brucei characteristic structural modifications. The GPI collection will be used to assess the effect of galactosylation and phosphorylation on T. brucei GPI immunomodulatory activity, and to perform an epitope mapping of this complex glycolipid as potential diagnostic marker for Trypanosomiasis. A strategy for the synthesis of a complete α-tetragalactoside using the 2-naphthylmethyl protecting group and for subsequent attachment of GPI fragments to peptides is presented.

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“…In 2006, Nikolaev's group demonstrated a strategy utilizing benzoyl ester for permanent protection of hydroxyl groups for the synthesis of GPI from T. cruzi containing unsaturated lipids . More recently, strategies that employ an acid‐labile protecting group such as para ‐methoxybenzyl (PMB) and 2‐naphthylmethyl (Nap) have been developed. Although these strategies have enabled the syntheses of various functionalized GPIs, there are some limitations to their use due to the undesired saponification of fatty acid ester under basic conditions and the undesirable need for the removal of acid‐labile protecting groups under acidic conditions .…”

Section: Introductionmentioning

confidence: 99%

Employing BINOL‐Phosphoroselenoyl Chloride for Selective Inositol Phosphorylation and Synthesis of Glycosyl Inositol Phospholipid from Entamoeba histolytica

Aiba

Suehara

Choy

et al. 2017

Chemistry A European J

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The chemical synthesis of glycosyl inositol phospholipids from Entamoeba histolytica is reported. The key feature of this synthesis is a regioselective phosphorylation reaction that occurs through desymmetrization of a myo-inositol derivative with phosphoroselenoyl chloride. A new protecting-group strategy was developed that utilizes allyl and alloc groups to synthesize complex glycolipids bearing unsaturated lipids. These developments provided an efficient synthetic route for various complex inositol phospholipids and their analogues. Furthermore, the binding affinity of the synthetic inositol phospholipids with mouse CD1d molecules has been evaluated, as well as the immunostimulatory activity.

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Synthesis of glycosylphosphatidylinositol (GPI)-anchor glycolipids bearing unsaturated lipids

Cited by 18 publications

References 26 publications

Zwitterionic Character and Lipid Composition Determine the Behaviour of Glycosylphosphatidylinositol Fragments in Monolayers

Zwitterionic Character and Lipid Composition Determine the Behaviour of Glycosylphosphatidylinositol Fragments in Monolayers

Synthesis of Galactosylated Glycosylphosphatidylinositol Derivatives from Trypanosoma brucei

Employing BINOL‐Phosphoroselenoyl Chloride for Selective Inositol Phosphorylation and Synthesis of Glycosyl Inositol Phospholipid from Entamoeba histolytica

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