Environmentally responsive amino acid-bioconjugated dynamic covalent copolymer as a versatile scaffold for conjugation

Abstract

Biodynamers display the properties of biomolecules with the adaptive nature of dynamic covalent polymers and have great potential as "smart" materials. The bioconjugation of L-tyrosine hydrazide to the end of bisaldehyde-functionalized thermoresponsive copolymer chains via reversible acylhydrazone linkage generated a biodynamer with thermo/pH-responsive and adaptive features. Because of the introduction of amino acid end groups, the biodynamer had an isoelectric point (IEP) at pH 4.70 and possessed a pHdependent LCST. The properties of the biodynamer were tunable through chain exchange reactions with other hydrazine or hydrazide molecules. The biodynamer endowed biological recognition by exchange with biotin hydrazide. The complex formed by the biotinylated dynamer and streptavidin demonstrated pH-responsive features. Because of the versatile reactivity of the phenolic moiety, this biodynamer provided a reactive scaffold for further modification. The cyclic diazodicarboxamide was attached to the biodynamer through the tyrosine-click reaction. Protein bioconjugate with pH-responsive and adaptive features was prepared via HRP-catalyzed coupling reaction.

Noncovalent and Dynamic Covalent Chemistry Strategies for Driving Thermoresponsive Phase Transition with Multistimuli and Controlled Encapsulation/Release

“…Sanders reported a dynamic combinatorial library of oligomeric hydrazone receptors for the recognition of dihydrogen phosphate ion . Thermoresponsive acylhydrazone polymeric systems, including self-healing gels, adaptive dynamers, nanoparticle assembles, and micelles, have also been developed, such as in the works of Lehn, Fulton, , Liu, Qin, and others. − Most of these polymers display the LCST property and show response to pH change. Despite the popularity of acylhydrazone polymers, their multiresponsive control, particularly through supramolecular anion recognition, − has largely been overlooked.…”

Peroxidase-Mediated In Situ Fabrication of Multi-Stimuli-Responsive and Dynamic Protein Nanogels from Tyrosine-Conjugated Biodynamer and Ovablumin

“…Enzyme-mediated tyrosine coupling was employed for the generation of protein–protein heteroconjugations, , hyperbranched protein polymers, and protein–chitosan bioconjugations . We previously investigated the modification of bovine serum albumin (BSA) with tyrosine-conjugated biodynamer by HRP-catalyzed coupling reaction . In this paper, we describe a facile approach that allows in situ fabrication of multistimuli-responsive protein nanogels in the aqueous solution.…”

“…In order to tune the LCST of the copolymer to near body temperature, P­(DEGA- co -PEGA) ( M n 6200, Đ = 1.30) consisting of 80 mol % DEGA and 20 mol % PEGA was prepared. After removal of the thiocarbonylthio end group, the bisaldehyde-functionalized copolymer P­(DEGA- co -PEGA)-bisCHO (CP-bisCHO) bioconjugated with l -tyrosine hydrazide to obtain tyrosine-conjugated biodynamer CP- dyn -Tyr through the reversible acylhydrazone formation . In 1 H NMR spectrum, the characteristic signals of acylhydrazone were observed at δ 7.94 and 8.18 ppm, and the signals corresponding to tyrosine moiety appeared at δ 6.5, 7.0, and 9.1 ppm (Figure S1 in Supporting Information).…”

“…31 We previously investigated the modification of bovine serum albumin (BSA) with tyrosine-conjugated biodynamer by HRP-catalyzed coupling reaction. 32 In this paper, we describe a facile approach that allows in situ fabrication of multistimuli-responsive protein nanogels in the aqueous solution. Herein, OVA containing 10 tyrosine residues and 4 free thiol groups is chosen to conjugate with tyrosine-conjugated biodynamer by HRP-mediated oxidative coupling of tyrosine moieties.…”

“…After removal of the thiocarbonylthio end group, the bisaldehyde-functionalized copolymer P(DEGA-co-PEGA)-bis-CHO (CP-bisCHO) bioconjugated with L-tyrosine hydrazide to obtain tyrosine-conjugated biodynamer CP-dyn-Tyr through the reversible acylhydrazone formation. 32 In 1 H NMR spectrum, the characteristic signals of acylhydrazone were observed at δ 7.94 and 8.18 ppm, and the signals corresponding to tyrosine moiety appeared at δ 6.5, 7.0, and 9.1 ppm (Figure S1 in Supporting Information). The copolymer CP-bisCHO was thermoresponsive and had a LCST value of 40.5 °C.…”