Tawara, Maun H.Correa Chinea, Juan FranciscoLeire, EmmaDelgado González, BrunoParcero Bouzas, SamuelLiko, FlonjaFernández Megía, Eduardo2025-10-212025-10-212025Tawara, M. H., Correa, J., Leire, E., Gonzalez, B. D., Parcero-Bouzas, S., Liko, F., & Fernandez-Megia, E. (2025). Bioactive Polymeric Scaffolds: Multivalent Functionalization by Thermal Azide–Alkyne Cycloaddition with Alkynyl Dicarbamates. "Biomacromolecules". https://doi.org/10.1021/acs.biomac.5c000381525-7797https://hdl.handle.net/10347/43316Multivalency enables interactions with higher affinities and specificities than monovalent interactions. The strategy exploited by nature to modulate biorecognition has inspired the design of multivalent conjugates with therapeutic properties. However, chemical functionalization often requires coupling agents, additives, or metal catalysts that complicate isolation and purification. Herein, azide–alkyne cycloaddition (AAC) with alkynyl dicarbamates (Alk-R) is presented as a flexible, reliable, atom-economical, and user-friendly strategy for the multivalent functionalization of polymeric scaffolds. Alk-R functionalized with biologically relevant ligands have been prepared and used for the multivalent AAC functionalization of azide-bearing dendrimers and block copolymers. The resulting polymers with double multivalency reveal a platform for the development of bioinspired functional systems with promising applications in drug delivery: block copolymer micelles and multifunctional nanocarriers with synergistically integrated probes-ligands-drugs. The extension of this strategy to other ligands and scaffolds is expected to open up a wide range of therapeutic and diagnostic opportunities.engCopyright © 2025 American Chemical SocietyAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/DendronsFluorescenceFunctionalizationHydrocarbonsMicelles2306 Química orgánicajournal article10.1021/acs.biomac.5c000381526-4602open access