Elucidating the mechanisms of the molecular sieving phenomenon created by comb-shaped polymers grafted to a protein – a simulation study

Drossis, Nicole; Gauthier, Marc A.; Haan, Hendrick W. de

doi:10.1016/j.mtchem.2022.100861

Cited by 2 publications

(7 citation statements)

References 29 publications

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“…Polymers can adopt a massive number of conformations in solution, [17,18] and therefore the exposure of the coupling functionality to the reactive moiety at the protein can be compromised with high molecular weight polymers. In this sense, it is a matter of interest to understand how the protein and the polymer interact in solution through docking‐like models [19] …”

Section: Enzyme‐polymer Hybridsmentioning

confidence: 99%

“…The design of these gaps is relevant to impart substrate size‐selectivity to the enzyme, also known as the sieving effect. Only substrates smaller than the cut‐off size set by the polymer conformation will be transformed [19] . Moreover, the distribution of the polymers and therefore, the size of the gap can be computationally simulated [47,48] .…”

Section: Tuning the Catalytic Performance And The Stability With Tail...mentioning

confidence: 99%

“…In this sense, it is a matter of interest to understand how the protein and the polymer interact in solution through docking-like models. [19] N-terminal amino acids, reduced cysteines, and lysines can be considered as the most commonly targeted residues for chemical conjugation events. The selection of the targeted amino acids is performed considering the number of chains that are foreseen to be grafted (grafting density), their localization, and therefore the distribution of eventually grafted polymer chain, and the reactivity of the residues.…”

Section: Use Of Preformed Polymers For the Synthesis Of Epcs: Graftin...mentioning

confidence: 99%

“…Only substrates smaller than the cut-off size set by the polymer conformation will be transformed. [19] Moreover, the distribution of the polymers and therefore, the size of the gap can be computationally simulated. [47,48] The bulkiness of the polymers can also be harnessed to control the degradation of enzymes on demand.…”

Section: Effect Of the Size Position And Polymer Density On The Catal...mentioning

confidence: 99%

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Enzyme‐Polymer Conjugates for Tuning, Enhancing, and Expanding Biocatalytic Activity

Heredero

Beloqui

2023

ChemBioChem

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Combining polymers with functional proteins is an approach that has brought several successful stories in the field of biomedicine with PEGylated therapeutic proteins. The latest advances in polymer chemistry have facilitated the expansion of protein-polymer hybrids to other research areas such as biocatalysis. Polymers can impart stability and novel functionalities to the enzyme of interest, thereby improving the catalytic performance of a given reaction. In this review, we have revisited the main methodologies currently used for the synthesis of enzyme-polymer hybrids, unveiling the interplay between the configuration and the composition of the assembled structure and the eventual traits of the hybrid. Finally, the latest advances, such as the assembly of polymerbased chemoenzymatic nanoreactors and the use of deep learning methodologies to achieve the most suitable polymer compositions for catalysis, are discussed.

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Section: Enzyme‐polymer Hybridsmentioning

confidence: 99%

Section: Tuning the Catalytic Performance And The Stability With Tail...mentioning

confidence: 99%

Section: Use Of Preformed Polymers For the Synthesis Of Epcs: Graftin...mentioning

confidence: 99%

Section: Effect Of the Size Position And Polymer Density On The Catal...mentioning

confidence: 99%

See 2 more Smart Citations

Enzyme‐Polymer Conjugates for Tuning, Enhancing, and Expanding Biocatalytic Activity

Heredero

Beloqui

2023

ChemBioChem

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“…Innovations in utility and architecture continue to be reported, such as controlled and site-specific PEGylation for increasing enzyme stability ,, and protein grafting with PEG-derived, comb-shaped poly[oligo(ethylene glycol)] (pOEGMA) to impart stealth properties while minimizing anti-PEG antigenicity. , Hyper-PEGylation with high-density PEG brushes has also been used to prevent protein–surface interactions , and even to inhibit phagocytic cell uptake of ovalbumin nanocapsules . In recent years, enzymes grafted with PEG-brushes and combs have been used to selectively block protein–protein interactions while still allowing small molecule substrates to diffuse through to the active sitean effect known as molecular sieving. , The seminal work by Gauthier and co-workers showcased this size-based effect with chymotrypsin (CT) and l -asparaginase conjugates, respectively, using pOEGMA comb polymers. The authors noted that the sieving efficiency was affected by polymer molecular weight and conformation in solution.…”

Section: Introductionmentioning

confidence: 99%

Molecular Sieving with PEGylated Dendron-Protein Conjugates

et al. 2023

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A series of generation 3−5 dendrons based on a bis(2,2hydroxymethylpropionic acid) (bis-MPA) scaffold bearing three respective lengths of linear poly(ethylene glycol) at their periphery and a dibenzocyclooctyne unit at their core was prepared. These dendrons were appended to the surface of azide-decorated α-chymotrypsin (α-CT) via strain-promoted azide−alkyne cycloaddition to yield a library of dendron-protein conjugates. These conjugates were characterized by FT-IR and NMR spectroscopy and were imaged using cryo-electron microscopy. The activity of the PEGylated α-CT-dendron conjugates was investigated using a small molecule (benzoyl-L-tyrosine p-nitroanilide) as well as different proteins of different sizes and crystallinities (casein and bovine serum albumin) as substrates. It was found that the activity of the conjugates toward the small molecule was largely retained, while the activity toward the proteins was significantly diminished. Furthermore, the results indicate that for most of the conjugates the PEG length had a more pronounced impact on enzyme activity than the dendron generation. Overall, the highest sieving ratios were found for α-CT-dendron conjugates decorated with G3-PEG 2000 , G4-PEG 2000 , and G5-PEG 1000 , with the latter two structures offering the best combination of sieving ratio and small molecule activity.

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Elucidating the mechanisms of the molecular sieving phenomenon created by comb-shaped polymers grafted to a protein – a simulation study

Cited by 2 publications

References 29 publications

Enzyme‐Polymer Conjugates for Tuning, Enhancing, and Expanding Biocatalytic Activity

Enzyme‐Polymer Conjugates for Tuning, Enhancing, and Expanding Biocatalytic Activity

Molecular Sieving with PEGylated Dendron-Protein Conjugates

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