Parallel Synthesis and Screening of a Solid Phase Carbohydrate Library

Liang, Rui; Yan, Lin; Loebach, Jennifer; Min, Gao; Uozumi, Yasuhiro; Sekanina, Klara; Horan, Nina; Gildersleeve, Jeffrey C.; Thompson, Chris; Smith, Alastair; Biswas, Kaustav; Still, W. Clark; Kahne, Daniel

doi:10.1126/science.274.5292.1520

Cited by 291 publications

(162 citation statements)

References 21 publications

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“…The SPR results verified our previous findings that the selectivity of BP lectin for ligands 1 and 2 depends on the context of the carbohydrate ligands (6,7). The SPR experiments further suggested that the observed change in binding selectivity on going from solution to a TentaGel bead was not caused by a simple orientation effect.…”

Section: Measurement Of Protein Binding At Increasing Ligand Densitiessupporting

confidence: 77%

“…Initial experiments addressed whether the mixed SAMs were an appropriate model system to investigate specific interactions between surface-bound carbohydrates and proteins. Previous studies on TentaGel beads had shown that BP lectin recognizes ligands 1a and 2a in the presence of other structurally similar ligands, suggesting a high degree of specificity in the polyvalent interactions (6,7). Mixed SAMs presenting 1c (Fig.…”

Section: Mixed Sams As Model Systems For Assessing Protein Binding Tomentioning

confidence: 99%

“…Compound 5 was synthesized in three steps from CH 2 CHO(CH 2 CH 2 O) 6 H: (i) NaH, ClCH 2 C(O)NH-(CH 2 ) 6 NHBoc, THF, 0°C to room temperature (RT), 10 h; (ii) thiolacetic acid, 2,2Ј-azobisisobutyronitrile (AIBN), benzene, 80°C, 48 h; and (iii) 20% TFA͞CH 2 Cl 2 , RT, 4.5 h.…”

Section: Synthesis Of Compoundmentioning

confidence: 99%

“…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%

“…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).…”

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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.

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197

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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Section: Measurement Of Protein Binding At Increasing Ligand Densitiessupporting

confidence: 77%

Section: Mixed Sams As Model Systems For Assessing Protein Binding Tomentioning

confidence: 99%

Section: Synthesis Of Compoundmentioning

confidence: 99%