Recent Progress on Affibody-Based Supramolecular Architectures: Moving from Monomeric Constructs to Multivalent Assemblies

Hongfei Wang,Liqiang Wei,Chunyue Du,A. Kam,Shining Loo

Published 2025 in Pharmaceuticals

ABSTRACT

Affibody molecules have emerged as versatile protein engineering platforms due to their exceptional binding properties. These small (6.5 kDa) three-helix bundle proteins, derived from the Z-domain of Staphylococcal protein A, can be engineered to bind diverse molecular targets with high affinity and specificity. This structural and functional versatility has driven their applications in diagnostics, therapeutics, and biosensing. This review examines the evolution from monomeric affibody constructs to multivalent supramolecular assemblies, highlighting how this shift overcomes key limitations while expanding functionality. Recent advances in conjugation chemistry, scaffold engineering, and protein design have enabled sophisticated affibody-based architectures with enhanced pharmacokinetic profiles and multivalent binding capabilities, thereby improving their utility in targeted drug delivery, molecular imaging, and theranostics.

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