Synthesis of Multifunctional Protein‐Polymer Conjugates via Oxygen‐tolerant, Aqueous Copper‐Mediated Polymerization, and Bioorthogonal Click Chemistry

Abstract

Oxygen‐tolerant, aqueous copper‐mediated polymerization approaches are combined with click chemistry in either a sequential or a simultaneous manner, to enable the synthesis of multifunctional protein‐polymer conjugates. Propargyl acrylate (PgA) and propargyl methacrylate (PgMA) grafting from a bovine serum albumin (BSA) macroinitiator is thoroughly optimized to synthesize chemically addressable BSA‐poly(propargyl acrylate) and BSA‐poly(propargyl methacrylate) respectively. The produced multifunctional bioconjugates bear pendant terminal 1‐alkynes which can be readily post‐functionalized via both [3+2] Huisgen cycloaddition and thiol‐yne click chemistry under mild reaction conditions. Simultaneous oxygen‐tolerant, aqueous copper‐catalyzed polymerization, and click chemistry mediate the in situ multiple chemical tailoring of biomacromolecules in excellent yields.

Tailored Branched Polymer–Protein Bioconjugates for Tunable Sieving Performance

“…Protein–polymer conjugates play a crucial role in a wide range of biomedical and biotechnological applications. These hybrid materials combine the unique biological activities of proteins or enzymes with the advantageous chemical and physical properties of synthetic polymers. − For example, attaching polymers to the surface of proteins can preserve or enhance their enzymatic activity even under harsh conditions, prolong circulation time by reducing renal clearance, protect proteins from antibodies and digestive enzymes, and make them responsive to factors such as pH, light, and temperature. , Advanced synthetic techniques such as reversible deactivation radical polymerization (RDRP) − and “click” chemistry have been instrumental in obtaining well-defined bioconjugates. − In turn, the development of new analytical methods has improved the ability to determine the chemical structure and physical properties of bioconjugates . As a result, the synthesis of precisely engineered functional polymer bioconjugates has emerged as one of the central focuses in macromolecular engineering. − …”

“… 4 , 5 Advanced synthetic techniques such as reversible deactivation radical polymerization (RDRP) 6 − 11 and “click” chemistry have been instrumental in obtaining well-defined bioconjugates. 12 − 15 In turn, the development of new analytical methods has improved the ability to determine the chemical structure and physical properties of bioconjugates. 16 As a result, the synthesis of precisely engineered functional polymer bioconjugates has emerged as one of the central focuses in macromolecular engineering.…”

Dexterous green synthesis of Cu2O nanoparticles: An amenable catalyst for aqueous click reaction, antiproliferative, and wound healing applications

“…The aforementioned concepts open up novel possibilities for the click reaction's archetype, the copper‐catalyzed Huisgen 1,3‐dipolar cycloaddition of organic azides and alkynes. Azide‐alkyne cycloaddition (AAC) employs several popular Cu(I) systems, which include the CuSO 4 ‐ascorbate system, 16 Cu(I)/(II) and Cu‐coordination complex supported on ligands, 17 Cu(I)‐zeolite, 18 polymer‐supported Cu(I), 19 copper NPs, 20,21 magnetic Cu/Fe bimetallic NPs, 22 metallic copper turning, magnetic nano‐Fe 3 O 4 @‐TiO 2 /Cu 2 O, graphene/charcoal supported Cu 2 O NPs, 23 and dicopper‐substituted silicotungstate 24 . Although the aforementioned cycloaddition has been extensively investigated, the potential utilization of green synthesized copper oxide NPs in this reaction is scant, and there is still room for further research.…”