Synthesis of Sialyl Lewis X Mimetics and Related Structures Using the Glycosyl Phosphite Methodology and Evaluation of E-Selectin Inhibition

Lin, Chun Cheng; Shimazaki, Makoto; Heck, Marie‐Pierre; Aoki, Shin; Wang, Ruo; Kimura, Teiji; Ritzén, Helena; Takayama, Shuichi; Wu, Shih Hsiung; Weitz-Schmidt, Gabriel; Wong, Chi Huey

doi:10.1021/ja952265x

Cited by 93 publications

(19 citation statements)

References 74 publications

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“…Indeed, phage display technology has been used to identify a peptide sequence that interacts with the plant lectin concanavalin A, presumably through its carbohydrate recognition domain (36). The organic and medicinal chemistry literature is also replete with synthetic schemes and in vitro inhibition data (if not yet in vivo) for structural mimics of the glycan portions of the selectin counter-receptors (37). We can also anticipate other approaches to diminish selectin-dependent leukocyte recruitment, through pharmacological inhibition of induced selectin expression, for example, or via molecules that inhibit the activity of the glycosyltransferases required for leukocyte selectin ligand synthesis, or that block synthesis of nucleotide sugar substrates for these enzymes.…”

mentioning

confidence: 99%

Therapeutic inhibition of carbohydrate-protein interactions in vivo.

Lowe

Ward²

1997

J. Clin. Invest.

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mentioning

confidence: 99%

Therapeutic inhibition of carbohydrate-protein interactions in vivo.

Lowe

Ward²

1997

J. Clin. Invest.

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“…[14] A glycopeptide mimic of the SLe x tetrasaccharide containing fucose on a peptide scaffold had a greater than tenfold increased binding affinity for E-selectin. [117] There was no further significant increase in affinity when the ligands were immobilized in a polymeric multivalent arrangement in liposomes. [118] In another example, a high-affinity divalent adhesin ligand which contained aGal(1 34)aGal linked by peptide bonds to an aromatic nucleus was prepared for Streptococcus suis.…”

Section: Glycopeptides As Oligosaccharide Mimeticsmentioning

confidence: 96%

“…[134] For the E-selectin selectivity it was necessary to incorporate a hydroxyl group, which mimics the 4-hydroxyl group of the central Gal in SLe x , in addition to a Fuc-residue, and a carboxylate, to obtain ligands with greater than 10-fold increased activity over that of the SLe x tetrasaccharide. [117] One of the best ligands was obtained from Thr(a-Fuc)-OEt, which was first N-acylated with a hydroxyamino acid and then elongated with a diacid to furnish the acid mimic of the sialic acid carboxylate ( Figure 10). This approach was further developed as a solid-phase method where the molecule was linked to a solid support through the invariable fucosyl moiety.…”

Section: Parallel Synthesis Of Glycopeptide Arraysmentioning

confidence: 99%

Glycopeptide and Oligosaccharide Libraries

Hilaire

Meldal

2000

Angew. Chem. Int. Ed.

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Despite the burgeoning interest in the various biological functions and consequent therapeutic potential of the vast number of oligosaccharides found in nature on glycoproteins and cell surfaces, the development of combinatorial carbohydrate chemistry has not progressed as rapidly as expected. The reason for this imbalance is rooted in the difficulty of oligosaccharide assembly and analysis that renders synthesis a rather cumbersome endeavor. Parallel approaches that generate series of analogous compounds rather than real libraries have therefore typically been used. Since generally low affinity is obtained for interactions between carbohydrate receptors and modified oligosaccharides designed as mimetics of natural carbohydrate ligands, glycopeptides have been explored as alternative mimics. Glycopeptides have been proven in many cases to be superior ligands with higher affinity for a receptor than the natural carbohydrate ligand. High-affinity glycopeptide ligands have been found for several types of receptors including the E-, P-, and L-selectins, toxins, glycohydrolases, bacterial adhesins, and the mannose-6-phosphate receptor. Furthermore, the assembly of glycopeptides is considerably more facile than that of oligosaccharides and the process can be adapted to combinatorial synthesis with either glycosylated amino acid building blocks or by direct glycosylation of peptide templates. The application of the split and combine approach using ladder synthesis has allowed the generation of very large numbers of compounds which could be analyzed and screened for binding of receptors on solid phase. This powerful technique can be used generally for the identification and analysis of the complex interaction between the carbohydrates and their receptors.

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“…The 6-acyl participation strategy in galactosylations was utilized to prepare the α-anomer of disaccharide 12 by Wong and coworkers in 1996 (9). The galactosylation of trihydroxy galactoside 11 with α-galactosyl phosphite donor 10 bearing an 6-O-acetyl group was α-selective, yielding disaccharide 12 (α/β = 85:15) with an excess of the α-anomer (Scheme 4).…”

Section: B the Remote Participation In Glycopyranosylationsmentioning

confidence: 99%

Remote Participation of Protecting Groups at Remote Positions of Donors in Glycosylations

Kim

Suk

2011

TIGG

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Effects of potentially participating groups at remote positions of glycopyranosyl and glycofuranosyl donors on the glycosylation stereochemistry are reviewed. Substantial evidences in favor of the remote participation by protecting groups are presented and also included are a few reports opposed to the remote participation. A. IntroductionT h e p r o t e c t i n g g r o u p s i n t h e o l i g o s a c c h a r i d e synthesis are used to selectively block interfering functions as well as influence the reactivity and stereoselectivity in the glycosylation steps. The anchimeric assistance of a neighboring participating group such as an acyl group at the O-2 position of the glycosyl donor has been one of the most useful strategies for the stereoselective formation of 1,2-trans glycosides (1−5). The carbonyl functionality at the O-2 position of the glycosyl donor can attack an incipient oxonium ion to give a dioxonium ion. Nucleophilic attack by an acceptor to the opposite face of the dioxonium ion provides the 1,2-trans glycoside. When potentially participating groups are located at remote positions other than the O-2 position of glycosyl donors, the existence of the remote participation by the remote protecting groups in the glycosylation step has been controversial. Although numerous examples for glycosylations with glycosyl donors possessing potentially participating groups at remote positions can be found in the literature, most of them do not provide any information on the remote participation by protecting groups in glycosylations. There have been reports both in favor of and opposed to the remote participation by protecting groups in glycosylations. Herein we review the effects of potentially participating protecting groups at remote positions of glycopyranosyl and glycofuranosyl donors on the glycosylation stereochemistry. Further, we present substantial evidence in favor of the remote participation by protecting groups and also include a few reports that are opposed to remote participation.

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Synthesis of Sialyl Lewis X Mimetics and Related Structures Using the Glycosyl Phosphite Methodology and Evaluation of E-Selectin Inhibition

Cited by 93 publications

References 74 publications

Therapeutic inhibition of carbohydrate-protein interactions in vivo.

Therapeutic inhibition of carbohydrate-protein interactions in vivo.

Glycopeptide and Oligosaccharide Libraries

Remote Participation of Protecting Groups at Remote Positions of Donors in Glycosylations

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