Synthesis of a neoglycoprotein containing the Lewis X analogous trisaccharide β-d-GalpNAc-(1→4)[α-l-Fucp-(1→3)]-β-d-GlcpNAc

Bartek, J.; Müller, Renate; Kosma, Paul

doi:10.1016/s0008-6215(98)00082-2

Cited by 37 publications

(20 citation statements)

References 28 publications

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“…The accepted pathway for the biosynthesis of the sLe x and sLe a structures starts by sialylation of the type-2 and type-1 chain precursors, respectively, followed by fucosylation of the sialylated intermediates. [17][18][19][20][21] In embryogenesis, sialylation is an early phenomenon that appears at the beginning of cell differentiation and precedes fucosylation. 22 The step of fucosylation is then rate-limiting for the formation of sLe x/a in many different cell types and tissues.…”

Section: Discussionmentioning

confidence: 99%

“…The mixture was incubated for 16 hours at 37°C and the reaction was stopped by the addition of 3 ml of cold water and centrifuged. The supernatant was added to the Sep-Pak C 18 cartridge, the unreacted GDP-[ 14 C ]-fucose and its hydrolysis products were washed out with 25 ml of H 2 O. Radiolabeled reaction products were eluted with methanol and counted in a liquid scintillation counter.…”

Section: Measurement Of Fucosyltransferase Activitymentioning

confidence: 99%

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Relationship of Sialyl-Lewisx/a Underexpression and E-Cadherin Overexpression in the Lymphovascular Embolus of Inflammatory Breast Carcinoma

Alpaugh

Tomlinson

Yin

et al. 2002

The American Journal of Pathology

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Inflammatory breast carcinoma (IBC) isOur screening methods for certain types of breast cancer such as inflammatory breast cancer (IBC) have not impacted the disease's age-adjusted 5 year mortality because these types of breast cancer do not remain organconfined before they are detected. 1 One telltale sign of lack of organ confinement is the presence of lymphovascular invasion, a finding that is most pronounced in IBC. 2 Lymphovascular invasion is defined by tumor emboli within lymphovascular spaces. 3 These emboli have a unique microscopic appearance of compact clumps of tumor cells retracted away from the surrounding endothelial cell layer lining the lymphovascular space. The molecular determinants of this phenotype remain undefined. Recently our laboratory established a human SCID model of IBC (MARY-X) that exhibited florid lymphovascular tumor emboli in vivo and compact spheroids in vitro. 4,5 We have characterized, in part, the molecular basis of the IBC phenotype using this model. Our initial studies indicated that MARY-X overexpressed both Ecadherin and MUC1. 4 We chose to focus on E-cadherin initially and demonstrated that both the tumor cell emboli and the in vitro spheroids formed on the basis of an intact and overexpressed E-cadherin/␣,␤-catenin axis that mediated tumor cell adhesion analogous to the embryonic blastocyst. 5 Disruption of the E-cadherin/␣,␤-catenin axis with either anti-E-cadherin antibodies or E-cadherin dominant-negative mutant approaches caused complete disadherence of the tumor emboli in vivo. Furthermore in addition to these two manipulations, trypsin proteolysis and Ca ϩϩ depletion caused complete disadherence of the spheroids in vitro. In the present study we decided to investigate the role of overexpressed MUC1 and a possible mechanism that might explain the apparent lack of binding of the tumor embolus to the surrounding endothelium.

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Section: Discussionmentioning

confidence: 99%

Section: Measurement Of Fucosyltransferase Activitymentioning

confidence: 99%

Relationship of Sialyl-Lewisx/a Underexpression and E-Cadherin Overexpression in the Lymphovascular Embolus of Inflammatory Breast Carcinoma

Alpaugh

Tomlinson

Yin

et al. 2002

The American Journal of Pathology

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“…However, since fucosyl residues at O-3 of glucosamine units are known 16 to be unstable when treated in acidic conditions, this reduction was left to proceed at room temperature rather than heated to 50 or 60 o C. After 7 h of reaction at this temperature, TLC showed complete disappearance of the starting material and formation of one major and one minor product. The major product was identified as chloroacetamide 33 (79%), and the minor product was characterized as the fully reduced acetamide 34 isolated in 11% yield.…”

Section: Introductionmentioning

confidence: 99%

Challenging Deprotection Steps During the Synthesis of Tetra- and Pentasaccharide Fragments of the Le^aLe^x Tumor-Associated Hexasaccharide Antigen

Guillemineau

Auzanneau

2012

J. Org. Chem.

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We report the convergent synthesis of two novel tetrasaccharide and two novel pentasaccharide fragments of the Le(a)Le(x) TACA: the tetrasaccharides contain neither the galactose at the Le(a) nonreducing end nor the fucose at the Le(x) reducing end; the pentasaccharides only lack the galactose residue at the Le(a) nonreducing end. Two of the analogues were prepared as hexyl glycosides to be used in NMR experiments and as soluble inhibitors in binding studies and two as 6-aminohexyl glycosides to be conjugated to carrier proteins. Our strategy relied on stepwise extensions using excess monosaccharide glycosyl donors (trichloroacetimidates and thioglycosides) in sequential glycosylation reactions. The protecting groups were chosen to limit the number of deprotection steps required to obtain the final derivatives. While this strategy ensured that all glycosylation reactions proceeded in very good yields (70-84%), deprotection of the oligosaccharide intermediates was challenging. Global deprotection using Birch metal dissolving conditions did not remove the tert-butyldiphenylsilyl group, which indeed was incompatible with such reaction conditions. Attempts to remove the TBDPS with tetrabutylammonium fluoride was unsuccessful and led to a complex mixture of compounds that could not be separated. The desired hexyl and aminohexyl tetrasaccharides were finally obtained after four- and five-step deprotection sequences, respectively. Deprotection of the pentasaccharide intermediate to give the hexyl and aminohexyl analogues also led to unexpected results. Indeed, during Zemplén deacylation, a chloroacetamide chlorine atom was displaced by methoxide ions leading to the corresponding methoxyacetamide. Once the chloroacetamide was fully reduced to an acetamide the pentasaccharides were obtained in four and five steps, respectively.

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“…The synthesis of some only slightly modified Le" analogs containing Glc instead of GlcNAc [78], GalNAc instead of Gal [79], or 5-thiofucose instead of Fuc [ 801 has been similarly performed as described above using trichloroacetimidate donors. It has been found that sialylations are always crucial and expensive processes, therefore many syntheses for sLeX mimetics have been developed in which neuraminic acid is replaced by other acids (Scheme 18).…”

Section: Ga@( 1 -4)glcnacp-x Neuaca(2-3) Fuca(1-3)mentioning

confidence: 99%

Trichloroacetimidates

Schmidt¹,

Jung²

2000

Carbohydrates in Chemistry and Biology

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Synthesis of a neoglycoprotein containing the Lewis X analogous trisaccharide β-d-GalpNAc-(1→4)[α-l-Fucp-(1→3)]-β-d-GlcpNAc

Cited by 37 publications

References 28 publications

Relationship of Sialyl-Lewisx/a Underexpression and E-Cadherin Overexpression in the Lymphovascular Embolus of Inflammatory Breast Carcinoma

Relationship of Sialyl-Lewisx/a Underexpression and E-Cadherin Overexpression in the Lymphovascular Embolus of Inflammatory Breast Carcinoma

Challenging Deprotection Steps During the Synthesis of Tetra- and Pentasaccharide Fragments of the Le^aLe^x Tumor-Associated Hexasaccharide Antigen

Trichloroacetimidates

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Synthesis of a neoglycoprotein containing the Lewis X analogous trisaccharide β-d-GalpNAc-(1→4)[α-l-Fucp-(1→3)]-β-d-GlcpNAc

Cited by 37 publications

References 28 publications

Relationship of Sialyl-Lewisx/a Underexpression and E-Cadherin Overexpression in the Lymphovascular Embolus of Inflammatory Breast Carcinoma

Relationship of Sialyl-Lewisx/a Underexpression and E-Cadherin Overexpression in the Lymphovascular Embolus of Inflammatory Breast Carcinoma

Challenging Deprotection Steps During the Synthesis of Tetra- and Pentasaccharide Fragments of the LeaLex Tumor-Associated Hexasaccharide Antigen

Trichloroacetimidates

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Challenging Deprotection Steps During the Synthesis of Tetra- and Pentasaccharide Fragments of the Le^aLe^x Tumor-Associated Hexasaccharide Antigen