Controlling Superselectivity of Multivalent Interactions with Cofactors and Competitors

Autor: Tine Curk, Galina V. Dubacheva, Alain R. Brisson, Ralf P. Richter
Přispěvatelé: Northwestern University [Evanston], Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Leeds, Marie Skłodowska-Curie Fellowship 'ELNANO' (845032) to T.C., Marie Curie Career Integration Grant 'CELLMULTIVINT' (293803) to G.V.D., and European Research Council Starting Grant 'JELLY' (306435) and Biotechnology and Biological Sciences Research Council grant BB/T001631/1 to R.P.R., European Project: 306435,EC:FP7:ERC,ERC-2012-StG_20111012,JELLY(2012), European Project: 293803,EC:FP7:PEOPLE,FP7-PEOPLE-2011-CIG,CELLMULTIVINT(2012)
Rok vydání: 2022
Předmět:
Zdroj: Journal of the American Chemical Society
Journal of the American Chemical Society, 2022, 144 (38), pp.17346-17350. ⟨10.1021/jacs.2c06942⟩
JACS
ISSN: 1520-5126
0002-7863
Popis: International audience; 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.
Databáze: OpenAIRE
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