A convenient synthetic route to the disaccharide repeating-unit of peptidoglycan

Kantoci, Darko; Keglević, Dina; Derome, Andrew E.

doi:10.1016/0008-6215(87)80218-5

Cited by 19 publications

(10 citation statements)

References 31 publications

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“…Compound 13, bearing a phthalimido group at position C(2) instead of an acetamido group, was chosen to decrease the negative influence of intermolecular H-bonds between the OH group and the NH group of the amide function in the glycosylation process. 39,40 Formation of glycal and symmetrical disaccharide with the β head to head glycosidic bond similar to that found in β,β-trehalose from glycosyl donors of 2-deoxy-2-phthalimido-D-glucopyranose type has been described. Furthermore, 4-O-acetyl-1,5-anhydro-3,6-di-O-benzyl-2-deoxy-2-phthalimido-D-lyxo-hex-1-enitol (24) (25) were isolated as the reaction side products, i.e., the products of elimination and cross-reaction of a glycosyl donor.…”

Section: Resultsmentioning

confidence: 53%

“…[36][37][38] Glycosylation of 13 with glycosyl bromide 22 under the above-described conditions gave the required disaccharide 23 in a satisfactory yield of 48%. 39,40 Zempl en deacetylation of disaccharide 23 followed by glycosylation of the obtained compound 26 with glycosyl donor 15 afforded trisaccharide 27 in an overall yield of 51%. 39,40 Formation of glycal and symmetrical disaccharide with the β head to head glycosidic bond similar to that found in β,β-trehalose from glycosyl donors of 2-deoxy-2-phthalimido-D-glucopyranose type has been described.…”

Section: Resultsmentioning

confidence: 99%

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SyntheticN-Acetyl-d-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69⁺Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker

Ковальова¹,

Ledvina²,

Šaman³

et al. 2010

J. Med. Chem.

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On the basis of the highly branched ovomucoid-type undecasaccharide that had been shown previously to be an endogenous ligand for CD69 leukocyte receptor, a systematic investigation of smaller oligosaccharide mimetics was performed based on linear and branched N-acetyl-d-hexosamine homooligomers prepared synthetically using hitherto unexplored reaction schemes. The systematic structure-activity studies revealed the tetrasaccharide GlcNAcbeta1-3(GlcNAcbeta1-4)(GlcNAcbeta1-6)GlcNAc (compound 52) and its alpha-benzyl derivative 49 as the best ligand for CD69 with IC(50) as high as 10(-9) M. This compound thus approaches the affinity of the classical high-affinity neoglycoprotein ligand GlcNAc(23)BSA. Compound 68, GlcNAc tetrasaccharide 52 dimerized through a hydrophilic flexible linker, turned out to be effective in activating CD69(+) lymphocytes. It also proved efficient in enhancing natural killing in vitro, decreasing the growth of tumors in vivo, and activating the CD69(+) tumor infiltrating lymphocytes examined ex vivo. This compound is thus a candidate for carbohydrate-based immunomodulators with promising antitumor potential.

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Section: Resultsmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

SyntheticN-Acetyl-d-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69⁺Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker

Ковальова¹,

Ledvina²,

Šaman³

et al. 2010

J. Med. Chem.

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“…2-deoxy--d-glucopyranose} was prepared according the protocol introduced by Kantoci et al (1987) and papers cited therein, with some revisions (Fig. 3).…”

Section: Nag-nam Disaccharide Synthesismentioning

confidence: 99%

“…The same amount of substrate/digestion products was analysed in both cases. catalytic hydrogenation gave NAG-NAM (Kantoci et al, 1987;Keglevic et al, 1985).…”

Section: Nag-nam Disaccharide Synthesismentioning

confidence: 99%

The mechanism behind the selection of two different cleavage sites in NAG-NAM polymers

Mihelič

Vlahoviček-Kahlina

Renko

et al. 2017

IUCrJ

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Peptidoglycan is a giant molecule that forms the cell wall that surrounds bacterial cells. It is composed of alternating N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) residues connected by -(1,4)-glycosidic bonds and cross-linked with short polypeptide chains. Owing to the increasing antibiotic resistance against drugs targeting peptidoglycan synthesis, studies of enzymes involved in the degradation of peptidoglycan, such as N-acetylglucosaminidases, may expose new, valuable drug targets. The scientific challenge addressed here is how lysozymes, muramidases which are likely to be the most studied enzymes ever, and bacterial N-acetylglucosaminidases discriminate between two glycosidic bonds that are different in sequence yet chemically equivalent in the same NAG-NAM polymers. In spite of more than fifty years of structural studies of lysozyme, it is still not known how the enzyme selects the bond to be cleaved. Using macromolecular crystallography, chemical synthesis and molecular modelling, this study explains how these two groups of enzymes based on an equivalent structural core exhibit a difference in selectivity. The crystal structures of Staphylococcus aureus N-acetylglucosaminidase autolysin E (AtlE) alone and in complex with fragments of peptidoglycan revealed that N-acetylglucosaminidases and muramidases approach the substrate at alternate glycosidic bond positions from opposite sides. The recognition pocket for NAM residues in the active site of N-acetylglucosaminidases may make them a suitable drug target.

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“…363 The greater stability of the chloride counterpart, however, started a change in the trend and resulted in a number of syntheses employing this building block; for example, blood-group antigens, 364 peptidoglycans, 365 and disaccharide analogues of meonomycin. 366 Highly stable 2-phthalimidoglycosyl fluorides also found application in aminosugar synthesis.…”

Section: Disubstituted 2-amino-2-deoxyglycosyl Donorsmentioning

confidence: 98%

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

Bongat

Demchenko

2007

Carbohydrate Research

199

110

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A convenient synthetic route to the disaccharide repeating-unit of peptidoglycan

Cited by 19 publications

References 31 publications

SyntheticN-Acetyl-d-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69⁺Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker

SyntheticN-Acetyl-d-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69⁺Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker

The mechanism behind the selection of two different cleavage sites in NAG-NAM polymers

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

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A convenient synthetic route to the disaccharide repeating-unit of peptidoglycan

Cited by 19 publications

References 31 publications

SyntheticN-Acetyl-d-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69+Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker

SyntheticN-Acetyl-d-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69+Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker

The mechanism behind the selection of two different cleavage sites in NAG-NAM polymers

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

Contact Info

Product

Resources

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SyntheticN-Acetyl-d-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69⁺Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker

SyntheticN-Acetyl-d-glucosamine Based Fully Branched Tetrasaccharide, a Mimetic of the Endogenous Ligand for CD69, Activates CD69⁺Killer Lymphocytes upon Dimerization via a Hydrophilic Flexible Linker