Synthesis of 4” manipulated Lewis X trisaccharide analogues

Moore, Christopher; Auzanneau, France‐Isabelle

doi:10.3762/bjoc.8.126

Cited by 8 publications

(10 citation statements)

References 71 publications

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“…The starting pyranosides 6-18 were either prepared according to known methods (7, 8 8, 8 9, 9 10, 10 11, 11 13, 12 14, 13 16, 8 17, 10 18 10 ) or were available commercially (6,12,15). The acid-promoted per-O-sulfation was performed under typical conditions for the PIF rearrangement.…”

Section: Letter Syn Lettmentioning

confidence: 99%

The Pyranoside-into-Furanoside Rearrangement of Alkyl Glycosides: Scope and Limitations

Krylov¹,

Argunov²,

Vinnitskiy³

et al. 2016

Synlett

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The pyranoside-into-furanoside (PIF) rearrangement was recently reported as a useful tool for the synthesis of furanoside-containing complex oligosaccharides. Until now, this transformation has only been described for some protected allyl-β-D-galactosides and one L-fucoside. In this communication its applicability is expanded. The formation of furanosides was observed under acid-promoted sulfation for a series of galactosides with varying alkyl substituents at the anomeric position as well as for several fucosides and glucosides. Meanwhile, furanoside formation was not detected in the case of mannopyranosides. The different reactivity of substrates was explained by values of activation barriers of endocyclic C1-O5 bond cleavage calculated by ab initio RHF methods. The reported results clarify the scope and limitations of the PIF rearrangement, which is important for its application in the synthesis of carbohydrate structures of practical meaning.

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Section: Letter Syn Lettmentioning

confidence: 99%

The Pyranoside-into-Furanoside Rearrangement of Alkyl Glycosides: Scope and Limitations

Krylov¹,

Argunov²,

Vinnitskiy³

et al. 2016

Synlett

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“…The affinity of the mAb 1G5F6 for Le x was compared with its affinity for the 40-OH modified Le x analogues 10-13 ( Fig. 8) (16). The 40-methoxy Le x analogue 10 (downward triangle) showed no inhibition of the Le x binding to 1G5F6, even at high concentrations (..500 mM), suggesting that the methyl group led to unfavorable steric interactions within the binding site (Table I, entry 6) (42,46).…”

Section: Binding Studies With Analogues 5-13 and Mab 1g5f6mentioning

confidence: 99%

Recognition of Lewis X by Anti-Lex Monoclonal Antibody 1G5F6

Jegatheeswaran

Auzanneau

2019

The Journal of Immunology

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mAbs directed toward the Lewis X (Lex) determinant have been shown to display different specificities, depending on the presentation of Lex to the immune system. Of interest is the murine anti-Lex mAb 1G5F6, generated against the O chain polysaccharide of Helicobacter pylori that contains polymeric Lex structures. The mAb was found to have a higher affinity for polymeric Lex over monomeric Lex. In this study, we explore the recognition of monomeric Lex by 1G5F6 using a panel of Lex analogues in which N-acetyl-d-glucosamine, l-fucose, or d-galactose (D-Gal) are replaced with d-glucose and/or l-rhamnose. Our studies show that all analogues were weaker inhibitors than the Lex Ag, indicating that all three residues are essential in the recognition of Lex by mAb 1G5F6. We explored the involvement of 4″-OH of d-Gal in the binding with 1G5F6 using a panel of 4″-modified Lex analogues. Although the 4″-OH is only involved in a weak polar interaction, we conclude that the D-Gal residue in Lex is primarily involved in aromatic stacking interactions with the Ab binding site. We compared these results to our work with mAb SH1. Although stacking interactions between D-Gal and an aromatic residue was also suggested for SH1, an H-bond involving the 4″-OH was identified that is not found in the binding of 1G5F6 to Lex. Thus, anti-Lex mAbs SH1 and 1G5F6 bind to Lex in different manners, even though the hydrophobic patch displayed by the β-galactoside in Lex is essential in both cases for their binding to Lex.

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“…Given the lack of inhibition observed for GlcLe x 16 and the lack of binding of the (GDimLe x ) 16 -BSA conjugate in our titration experiments ( Figure 2 ), we investigated the importance of the galactosyl 4-OH group for recognition by SH2 using the previously described [ 57 ] analogues 19 – 22 in competitive binding experiments. In these analogues, the galactosyl 4-OH is either methylated (4″-MeOLe x , 19 ), deoxygenated (4″-HLe x , 20 ), or replaced by a halogen in the 4″-ClLe x ( 21 ) and 4″-FLe x ( 22 ) ( Figure 7 ).…”

Section: Resultsmentioning

confidence: 99%

Recognition of Dimeric Lewis X by Anti-Dimeric Lex Antibody SH2

et al. 2020

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The carbohydrate antigen dimeric Lewis X (DimLex), which accumulates in colonic and liver adenocarcinomas, is a valuable target to develop anti-cancer therapeutics. Using the native DimLex antigen as a vaccine would elicit an autoimmune response against the Lex antigen found on normal, healthy cells. Thus, we aim to study the immunogenic potential of DimLex and search internal epitopes displayed by DimLex that remain to be recognized by anti-DimLex monoclonal antibodies (mAbs) but no longer possess epitopes recognized by anti-Lex mAbs. In this context, we attempted to map the epitope recognized by anti-DimLex mAb SH2 by titrations and competitive inhibition experiments using oligosaccharide fragments of DimLex as well as Lex analogues. We compare our results with that reported for anti-Lex mAb SH1 and anti-polymeric Lex mAbs 1G5F6 and 291-2G3-A. While SH1 recognizes an epitope localized to the non-reducing end Lex trisaccharide, SH2, 1G5F6, and 291-2G3-A have greater affinity for DimLex conjugates than for Lex conjugates. We show, however, that the Lex trisaccharide is still an important recognition element for SH2, which (like 1G5F6 and 291-2G3-A) makes contacts with all three sugar units of Lex. In contrast to mAb SH1, anti-polymeric Lex mAbs make contact with the GlcNAc acetamido group, suggesting that epitopes extend further from the non-reducing end Lex. Results with SH2 show that this epitope is only recognized when DimLex is presented by glycoconjugates. We have reported that DimLex adopts two conformations around the β-d-GlcNAc-(1→3)-d-Gal bond connecting the Lex trisaccharides. We propose that only one of these conformations is recognized by SH2 and that this conformation is favored when the hexasaccharide is presented as part of a glycoconjugate such as DimLex-bovine serum albumin (DimLex-BSA). Proper presentation of the oligosaccharide candidate via conjugation to a protein or lipid is essential for the design of an anti-cancer vaccine or immunotherapeutic based on DimLex.

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Synthesis of 4” manipulated Lewis X trisaccharide analogues

Cited by 8 publications

References 71 publications

The Pyranoside-into-Furanoside Rearrangement of Alkyl Glycosides: Scope and Limitations

The Pyranoside-into-Furanoside Rearrangement of Alkyl Glycosides: Scope and Limitations

Recognition of Lewis X by Anti-Lex Monoclonal Antibody 1G5F6

Recognition of Dimeric Lewis X by Anti-Dimeric Lex Antibody SH2

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