Switching enzyme activity by a temperature responsive inhibitor modified polymer

Rottke, Falko O.; Heyne, Marie-Victoria; Reinicke, Stefan

doi:10.1039/c9cc09385k

Cited by 12 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reversible nature of these bonds allowed the enzyme-polymer conjugate to dissociate back to native enzymes without any remnants of the polymers, leading to total recovery of the structure and function of enzymes. [102] For example, Weil et al [48] established an acid responsive dendritic core-shell system which can selfassemble to a supramolecular dendrimer to provide steric protection for enzymes (trypsin, papain, and DNase I). To establish this hybrid, the native enzymes were first functionalized with boronic acid derivatives, followed by click reaction with salicyl hydroxamates modified dendron.…”

Section: Tumor Therapymentioning

confidence: 99%

Weaving Enzymes with Polymeric Shells for Biomedical Applications

Blum

et al. 2021

Advanced Materials

View full text Add to dashboard Cite

the most common administration method. However, the sizes of most enzymes are smaller than the kidney filtration threshold (50-60 kDa), resulting in fast renal clearance and short half-lives. [5] Also, limited by its hydrophilicity and large molecular weight, it is difficult for exogenous enzyme macromolecules to pass through the cell membrane to effectively catalyze intracellular target reactions. [6] To date, most of the clinical protein therapeutics were explored toward extracellular targets owing to the low translocation efficiency. [7] However, for enzyme therapeutics, especially for the enzyme replacement therapy, intracellular delivery is considered critical for effective therapy. [8] Typically, even if a number of enzymes are transfected into

show abstract

Section: Tumor Therapymentioning

confidence: 99%

Weaving Enzymes with Polymeric Shells for Biomedical Applications

Blum

et al. 2021

Advanced Materials

View full text Add to dashboard Cite

show abstract

“…Precise regulation of the enzymatic activity has been of great interest because of its potential applications in the fields of sensors, biomedicine, and bioelectronics [1] . Photochemical regulation can control the enzymatic activity on demand given its unique advantage in terms of high spatiotemporal resolution [2] .…”

Section: Introductionmentioning

confidence: 99%

“…Precise regulation of the enzymatic activity has been of great interest because of its potential applications in the fields of sensors, biomedicine, and bioelectronics. [1] Photochemical regulation can control the enzymatic activity on demand given its unique advantage in terms of high spatiotemporal resolution. [2] In recent years, great advances have been made in controlling the functions of biomacromolecules using a photoprotecting group such as nitrobenzene and its derivatives.…”

Section: Introductionmentioning

confidence: 99%

A Noncovalent Photoswitch for Photochemical Regulation of Enzymatic Activity

Chai

Zhao

et al. 2022

Angewandte Chemie

View full text Add to dashboard Cite

Photochemical regulation provides a promising approach for controlling enzyme activity on demand owing to its high spatiotemporal resolution. However, reversible regulation of the enzyme activity by light usually requires genetic mutations and covalent modifications of the target enzymes, which may lead to irreversible changes in the enzyme structure and subsequent loss of the enzymatic activity. Herein, we have developed a novel strategy based on a polymeric inhibitor-encapsulated enzyme, which noncovalently anchors the azobenzene-modified inhibitors to the enzyme active site, thereby achieving reversible control of the activity of native enzymes using light. As neither genetic mutation nor chemical modification of enzymes is required for this method, negligible loss of the enzymatic activity was observed for the encapsulated enzymes compared to their native counterparts. Thus, this approach has demonstrated a promising strategy for achieving reversible regulation of the activity of native enzymes.

show abstract

“…(see, e.g., Refs. [ 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 ] and references therein). Among enzymes, α-chymotrypsin (CT), a peptide bond cleaving serine protease enzyme, is one of the most widely investigated proteins in terms of its bioconjugation with a variety of polymers and applications in bioengineering [ 106 , 114 , 115 , 116 , 117 , 118 , 119 , 120 ].…”

Section: Introductionmentioning

confidence: 99%

Thermoresponsive Poly(N,N-diethylacrylamide-co-glycidyl methacrylate) Copolymers and Its Catalytically Active α-Chymotrypsin Bioconjugate with Enhanced Enzyme Stability

et al. 2021

View full text Add to dashboard Cite

Responsive (smart, intelligent, adaptive) polymers have been widely explored for a variety of advanced applications in recent years. The thermoresponsive poly(N,N-diethylacrylamide) (PDEAAm), which has a better biocompatibility than the widely investigated poly(N,N-isopropylacrylamide), has gained increased interest in recent years. In this paper, the successful synthesis, characterization, and bioconjugation of a novel thermoresponsive copolymer, poly(N,N-diethylacrylamide-co-glycidyl methacrylate) (P(DEAAm-co-GMA)), obtained by free radical copolymerization with various comonomer contents and monomer/initiator ratios are reported. It was found that all the investigated copolymers possess LCST-type thermoresponsive behavior with small extent of hysteresis, and the critical solution temperatures (CST), i.e., the cloud and clearing points, decrease linearly with increasing GMA content of these copolymers. The P(DEAAm-co-GMA) copolymer with pendant epoxy groups was found to conjugate efficiently with α-chymotrypsin in a direct, one-step reaction, leading to enzyme–polymer nanoparticle (EPNP) with average size of 56.9 nm. This EPNP also shows reversible thermoresponsive behavior with somewhat higher critical solution temperature than that of the unreacted P(DEAAm-co-GMA). Although the catalytic activity of the enzyme–polymer nanoconjugate is lower than that of the native enzyme, the results of the enzyme activity investigations prove that the pH and thermal stability of the enzyme is significantly enhanced by conjugation the with P(DEAAm-co-GMA) copolymer.

show abstract

Switching enzyme activity by a temperature responsive inhibitor modified polymer

Abstract: A thermoresponsive NIPAAm-based polymer is combined with the selective acetylcholinesterase inhibitor tacrine in order to create a strict in sense on/off switch for enzyme activity.

Cited by 12 publications

References 22 publications

Weaving Enzymes with Polymeric Shells for Biomedical Applications

Weaving Enzymes with Polymeric Shells for Biomedical Applications

A Noncovalent Photoswitch for Photochemical Regulation of Enzymatic Activity

Thermoresponsive Poly(N,N-diethylacrylamide-co-glycidyl methacrylate) Copolymers and Its Catalytically Active α-Chymotrypsin Bioconjugate with Enhanced Enzyme Stability

Contact Info

Product

Resources

About