The Cluster Glycoside Effect

Lundquist, Joseph J.; Toone, Eric J.

doi:10.1021/cr000418f

Cited by 1,472 publications

(1,203 citation statements)

References 206 publications

(274 reference statements)

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“…Their multivalent presentation in microdomains of the plasma membrane is important to acquire strong affinity of an oligosaccharide toward its ligand in carbohydrate-protein interactions, often called the cluster glycoside effect (31). Thus, the clustered assembly in microdomains renders gangliosides excellent candidates for tumor targeting employing lectins, toxins, or monoclonal antibodies directed toward tumor-associated gangliosides.…”

Section: Discussionmentioning

confidence: 99%

Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer

Distler

Souady²,

Hülsewig³

et al. 2008

Molecular Cancer Therapeutics

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Pancreatic adenocarcinoma confers one of the highest mortality rates in malignant human tumors with very poor prognosis. Because as yet no treatments are available that produce a substantial survival benefit for this fatal neoplasia, new therapeutic concepts are urgently required to support cancer standard treatment. In search of tumorassociated gangliosides with therapeutic background, we probed a random collection of cancerous and adjacent normal postoperative tissue samples from 38 patients for the expression of CD75s-and iso-CD75s-gangliosides. We exhaustively analyzed the expression of CD75s-1-ganglioside (IV 6 Neu5Ac-nLc4Cer) and structurally closely related iso-CD75s-1-ganglioside (IV 3 Neu5Ac-nLc4Cer) by means of immunohistology of cryosections and semiquantitative TLC of tissue lipid extracts combined with mass spectrometry. CD75s-1-and iso-CD75s-1-ganglioside showed an elevated expression in 42% and 66% of the tumors, respectively, indicating a significant association with neoplastic transformation (P = 0.001). Thus, increased expression of CD75s-1-and iso-CD75s-1-gangliosides renders these cell surface molecules promising candidates for oncologic applications. Further statistical analysis revealed a significant enhancement of CD75s-1-ganglioside in the group of less differentiated tumors (grade >2) suggesting this ganglioside as a potential marker for poor differentiation. The CD75s-specific antitumor drug rViscumin, which represents the recombinant counterpart of the ribosome-inactivating lectin viscumin, has successfully passed clinical phase I trials and provides an opportunity for treating pancreatic cancer. Consequently, if an enhanced expression is existent in malignant tissues, we propose the targeting of CD75s-gangliosides with rViscumin as a novel potential strategy in adjuvant treatment of pancreatic malignancies. [Mol Cancer Ther 2008;7(8):2464 -75]

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Section: Discussionmentioning

confidence: 99%

Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer

Distler

Souady²,

Hülsewig³

et al. 2008

Molecular Cancer Therapeutics

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“…91 Nevertheless, the only polymeric ligands synthesised so far which seem to bind through an intramolecular mechanism are those prepared by Kanai et al 110 (Fig. 7).…”

Section: Multivalent Ligandsmentioning

confidence: 99%

Lectins: Tools for the Molecular Understanding of the Glycocode

2005

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Recent progress in glycobiology has revealed that cell surface oligosaccharides play an essential role in recognition events. More precisely, these saccharides may be complexed by lectins, carbohydrate-binding proteins other than enzymes and antibodies, able to recognise sugars in a highly specific manner. The ubiquity of lectin-carbohydrate interactions opens enormous potential for their exploitation in BA (1993) and DPhil (1996) T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y

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“…1 Chemists have made use of this concept in various contexts. [2][3][4][5][6][7][8][9] The binding ability of multivalent agents is influenced by the number, size and orientation of the binding sites, as well as the shape, orientation and flexibility of the scaffold to which monomeric ligands are attached. Theoretically, the largest gain of binding affinity for a given ligand-receptor interaction is expected for a perfect fit of the ligands to the binding epitope.…”

Section: Introductionmentioning

confidence: 99%

Rigid Multivalent Scaffolds Based on Adamantane

et al. 2008

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We present two new synthetic strategies to rigid multivalent scaffolds of the general structure 1 based on adamantane. Both routes start from arylated adamantane derivatives and give the target compounds 12 and 18 in 5 and 7 steps, respectively. These scaffolds have been designed for the assembly of multivalent binders for cell surface epitopes. The adamantane nucleus exposes three carboxylic acid groups in a well defined tripodal geometry for conjugation of targeting ligands. In addition, an amino group at the fourth bridgehead position provides a flexible linker for attachment of effector molecules such as contrast agents, radiotracers, or cytotoxins without interfering with the cell binding process.

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The Cluster Glycoside Effect

Cited by 1,472 publications

References 206 publications

Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer

Tumor-associated CD75s- and iso-CD75s-gangliosides are potential targets for adjuvant therapy in pancreatic cancer

Lectins: Tools for the Molecular Understanding of the Glycocode

Rigid Multivalent Scaffolds Based on Adamantane

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