Why does targeting differences in receptor population require multivalent effects?

Stefano Angioletti-Uberti

doi:10.1016/j.cossms.2026.101271

Why does targeting differences in receptor population require multivalent effects?

2026-06-04

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Stefano Angioletti-Uberti *

DOI：10.1016/j.cossms.2026.101271

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• Receptors are often present on various cell types, but at different levels of expression. • Multivalent binding is a necessary condition to tell apart targets based on receptors expression levels. • Multivalent selectivity arises from non-linear effect due to the binding entropy without the need for cooperativity. • Indifferent binding (multiple ligands but only one can be bound at any time) is indistinguishable from monovalent binding. • Various antibody-based targeting strategies suffer from off-target effects because they are not multivalent.

Why does targeting differences in receptor population require multivalent effects?

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