CURK, Tine; DUBACHEVA, Galina V.; BRISSON, Alain R.; RICHTER, Ralf P.

doi:10.1021/jacs.2c06942

DUBACHEVA, Galina V.
Chimie et Biologie des Membranes et des Nanoobjets [CBMN]

BRISSON, Alain R.

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Journal of the American Chemical Society. 2022-09-28, vol. 144, n° 38, p. 17346-17350

Resumen en inglés

Moieties that compete with multivalent interactions or act as cofactors are common in living systems, but their effect on multivalent binding remains poorly understood. We derive a theoretical model that shows how the superselectivity of multivalent interactions is modulated by the presence of cofactors or competitors. We find that the role of these participating moieties can be fully captured by a simple rescaling of the affinity constant of the individual ligand–receptor bonds. Theoretical predictions are supported by experimental data of the membrane repair protein annexin A5 binding to anionic lipid membranes in the presence of Ca2+ cofactors and of the extracellular matrix polysaccharide hyaluronan (HA) binding to CD44 cell surface receptors in the presence of HA oligosaccharide competitors. The obtained findings should facilitate understanding of multivalent recognition in biological systems and open new routes for fine-tuning the selectivity of multivalent nanoprobes in medicinal chemistry.< Leer menos

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https://oskar-bordeaux.fr/handle/20.500.12278/201713

DOI

http://dx.doi.org/10.1021/jacs.2c06942

Proyecto europeo

Biomolecular Hydrogels – from Supramolecular Organization and Dynamics to Biological Function
Combining supramolecular chemistry, physico-chemical characterization and theoretical modeling to understand multivalent interactions at the cell-hyaluronan matrix interface

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CBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248

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Controlling Superselectivity of Multivalent Interactions with Cofactors and Competitors

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Resumen en inglés

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DOI

Proyecto europeo

Centros de investigación