Practical Synthesis of Starburst PAMAM α-Thiosialodendrimers for Probing Multivalent Carbohydrate−Lectin Binding Properties

Zanini, Diana; Roy, René

doi:10.1021/jo972061u

Cited by 116 publications

(78 citation statements)

References 30 publications

(34 reference statements)

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“…Carbohydrate-protein binding events usually involve several simultaneous contacts between carbohydrates that are clustered on cell surfaces and protein receptors that contain multiple carbohydrate-binding sites. Numerous studies on model systems have demonstrated that polyvalent displays of carbohydrates can lead to remarkably high binding avidities (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Because avidity and specificity are not necessarily correlated (6,7), however, polyvalency does not completely resolve the paradox of how marginally selective carbohydrate-binding interactions can produce highly specific responses.…”

mentioning

confidence: 99%

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Nonstatistical binding of a protein to clustered carbohydrates

Horan

Yan

Isobe

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

198

163

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Carbohydrate-derivatized self-assembled monolayers (SAMs) are used as a model system to address issues involving cell-surface carbohydrate-protein interactions. Here we examine the influence of carbohydrate surface density on protein-binding avidity. We show that the binding selectivity of Bauhinia purpurea lectin switches from one carbohydrate ligand to another as the surface density of the carbohydrate ligands increases from values of sugar Ϸ 0.1-1.0. Polyvalent binding is possible at all surface densities investigated; hence, the switch in selectivity is not due simply to the achievement of a critical density that permits polyvalent contacts. Instead, secondary interactions at high surface densities promote a switch in carbohydrate-binding selectivity. These findings may have implications for how changes in the composition and the density of cell-surface carbohydrates influence biological recognition processes and regulatory pathways. The patterns of expression of cell-surface carbohydrates change during development and differentiation (1-3). Changes in the composition of cell-surface carbohydrates also occur during oncogenesis and metastasis (4, 5). Although the biological functions of cell-surface carbohydrates are still incompletely defined, it is believed that they are somehow involved in signaling pathways that determine the temporal and spatial identity of cells. How changing patterns of cell-surface carbohydrates are linked to cell growth and differentiation is not understood.The early steps in cell-surface carbohydrate-mediated cellular processes are presumed to involve binding events between carbohydrates and receptors in the plasma or on the surface of other cells. Because these binding events are linked to specific cellular responses, one might expect them to be highly specific. However, studies in solution have shown that carbohydrateprotein binding interactions have dissociation constants that are typically in the mM range and that different carbohydrate ligands have similar affinities for the same protein receptor. If carbohydrates bind weakly and with poor selectivity, how can they mediate specific cellular processes?This paradox has been partially explained by the phenomenon of polyvalency. Carbohydrate-protein binding events usually involve several simultaneous contacts between carbohydrates that are clustered on cell surfaces and protein receptors that contain multiple carbohydrate-binding sites. Numerous studies on model systems have demonstrated that polyvalent displays of carbohydrates can lead to remarkably high binding avidities (6-16). Because avidity and specificity are not necessarily correlated (6, 7), however, polyvalency does not completely resolve the paradox of how marginally selective carbohydrate-binding interactions can produce highly specific responses.Two mechanisms have been proposed to explain how specificity can be achieved in cell-surface carbohydrate-binding interactions. In one mechanism, polyvalent carbohydrate-protein interactions facilitate the adhesion of cells. T...

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confidence: 99%

“…Simplified model systems are usually used to study polyvalent carbohydrate-protein interactions (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). We recently demonstrated that carbohydrates presented on TentaGel beads exhibit polyvalent binding and may therefore be useful as model systems to investigate the interactions of carbohydrates on surfaces (6, 7).…”

mentioning

confidence: 99%

Nonstatistical binding of a protein to clustered carbohydrates

Horan

Yan

Isobe

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

198

163

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“…[9] Lindhorst et al [10] and Cloninger et al [11] have reported mannosyl-persubstituted glycoPAMAM dendrimers, [10,11] whereas Roy et al [8,12] have synthesized mannosyl-, [12a] lactosyl-, [12b] sialosyl- [8] and T-antigen-persubstituted [12c] glycoPAMAM dendrimers by coupling with the respective glycosyl donors and the free amines of the PAMAM dendrimers. Glucosyl-, lactosyl-, and sialosyl-persubstituted aminoxy PAMAM dendrimers have also been reported.…”

Section: Introductionmentioning

confidence: 99%

“…To examine the effectiveness of the enzyme CDP, a cellobiosylated dimer and trimer, as well as cellobiose-coated PAMAM dendrimers possessing 4, 8,16,32 and 64 cellobiose units at the PAMAM dendrimer outer surface, were synthesized by conjugation of dendrimer free amine with the free carboxylic acid moiety attached at the reducing end of cellobiose in the presence of BOP [15] reagent and used as acceptor substrates for that enzyme.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of a Cellobiosylated Dimer and Trimer and of Cellobiose‐Coated Polyamidoamine (PAMAM) Dendrimers to Study Accessibility of an Enzyme, Cellodextrin Phosphorylase

2003

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To examine the accessibility of the enzyme cellodextrin phosphorylase (CDP) towards multivalent cluster carbohydrates, the cellobiosylated dimer 10 and trimer 12, as well as the cellobiose-coated PAMAM dendrimers 14, 16, 18, 20 and 22, with four, eight, sixteen, thirty-two and sixty-four cellobiose units at the outer surface of PAMAM dendrimers, respectively, have been synthesized for the first time and used as acceptor substrates for the enzyme CDP. It was found that CDP was able to transfer a glucosyl moiety from glucose-1-phosphate (Glc-1-P) into these synthesized cluster cellobiosylated glycoconjugates and cellobiose-coated PAMAM dendrimers, which were thus acceptor substrates for CDP. It was

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Solid-phase dendrimer synthesis

1998

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Dendrimers are highly ordered, hyperbranched polymers with potential for a whole range of chemical applications. Solution‐phase synthesis of dendrimers is often challenging, requiring long reaction times and nontrivial purification; solid‐phase methodology, on the other hand, enables reactions to be driven to completion by using a large excess of reagents with trivial purification. In this paper we show that polyamidoamine dendrimers may be synthesized conveniently and efficiently on a solid support, and that these molecules are of good homogeneity as characterized by 1H‐ and 13C‐nmr and electrospray mass spectrometry. These solid‐phase dendrimers were used as a bead loading amplification tool in the synthesis of a hexapeptide library (Xaa–Gly–Gly–Phe–Leu–Lys) to allow single bead analysis as well as allowing the efficient synthesis of two dendrimer conjugates (Leu–enkephalin–Lys and Chlorambucil). This demonstrated that peptides and small drug molecules can be grown directly onto the dendrimer or onto a linker attached to the dendrimer periphery, enhancing general dendrimer utility. © 1999 John Wiley & Sons, Inc. Biopoly 47: 381–396, 1998

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Practical Synthesis of Starburst PAMAM α-Thiosialodendrimers for Probing Multivalent Carbohydrate−Lectin Binding Properties

Cited by 116 publications

References 30 publications

Nonstatistical binding of a protein to clustered carbohydrates

Nonstatistical binding of a protein to clustered carbohydrates

Synthesis of a Cellobiosylated Dimer and Trimer and of Cellobiose‐Coated Polyamidoamine (PAMAM) Dendrimers to Study Accessibility of an Enzyme, Cellodextrin Phosphorylase

Solid-phase dendrimer synthesis

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