Next generation protein‐polymer conjugates

Russell, Alan J.; Baker, Stefanie L.; Colina, Coray M.; Figg, C. Adrian; Kaar, Joel L.; Matyjaszewski, Krzysztof; Simakova, Antonina; Sumerlin, Brent S.

doi:10.1002/aic.16338

Cited by 75 publications

(78 citation statements)

References 153 publications

(185 reference statements)

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“…Therefore, a rational design links the chemical properties of a particular polymer to its ultimate effect on the biological molecule. [ 5 ] New strategies and designs in protein conjugation techniques led to outstanding alternatives of the pioneering PEGylation, that is, the covalent attachment of poly(ethylene glycol). In particular, polyphosphoesters (PPEs), a chemical versatile class of polyesters that degrades hydrolytically and enzymatically, represent a promising novel and biocompatible alternative with maximum synthetic flexibility.…”

Section: Introductionmentioning

confidence: 99%

Insight into Protein–Polymer Conjugate Relaxation Dynamics: The Importance of Polymer Grafting

Russo

Pelosi

Wurm

et al. 2020

Macromolecular Bioscience

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The bio and chemical physics of protein–polymer conjugates are related to parameters that characterize each component. With this work, it is intended to feature the dynamical properties of the protein–polymer conjugate myoglobin (Mb)–poly(ethyl ethylene phosphate), in the ps and ns time scales, in order to understand the respective roles of the protein and of the polymer size in the dynamics of the conjugate. Elastic and quasi‐elastic neutron scattering is performed on completely hydrogenated samples with variable number of polymer chains covalently attached to the protein. The role of the polymer length in the protein solvation and internal dynamics is investigated using two conjugates formed by polymers of different molecular weight. It is confirmed that the flexibility of the complex increases with the number of grafted polymer chains and that a sharp dynamical transition appears when either grafting density or polymer molecular weight are high. It is shown that protein size is crucial for the polymer structural organization and interaction on the protein surface and it is established that the glass properties of the polymer change upon conjugation. The results give a better insight of the equivalence of the polymer coating and the role of water on the surface of proteins.

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Section: Introductionmentioning

confidence: 99%

Insight into Protein–Polymer Conjugate Relaxation Dynamics: The Importance of Polymer Grafting

Russo

Pelosi

Wurm

et al. 2020

Macromolecular Bioscience

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“…A hurdle in protein–polymer conjugate synthesis and characterization is heterogeneity. This makes characterization difficult 6 and it also impedes accurate measurements of activity and stability since unmodified protein may remain in the sample. Various chromatography techniques are typically used to purify conjugates including size exclusion, ion exchange, or high performance reverse phase chromatography, which all require instrumentation and user-knowledge.…”

Section: Resultsmentioning

confidence: 99%

“…Covalently attaching synthetic polymers to a protein, such as PEGylation, is one way to alter the bioactivity 2 , stability 3 , circulating half-life 4 , and immunogenicity 5 of the resultant protein–polymer conjugate. Polymer attachment site 6 , number of attachments 7,8 , polymer type 3,9 , polymer chain length 10,11 , and conjugation chemistry 12,13 are all variables that can be tuned to optimize the conjugate’s properties for a specific outcome, such as increased thermostability 14 or solubility. Protein solubility is especially important for therapeutic proteins, which can require concentrations as high as 100 mg/mL for effective dose administration.…”

Section: Introductionmentioning

confidence: 99%

Transforming protein-polymer conjugate purification by tuning protein solubility

et al. 2019

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Almost all commercial proteins are purified using ammonium sulfate precipitation. Protein-polymer conjugates are synthesized from pure starting materials, and the struggle to separate conjugates from polymer, native protein, and from isomers has vexed scientists for decades. We have discovered that covalent polymer attachment has a transformational effect on protein solubility in salt solutions. Here, protein-polymer conjugates with a variety of polymers, grafting densities, and polymer lengths are generated using atom transfer radical polymerization. Charged polymers increase conjugate solubility in ammonium sulfate and completely prevent precipitation even at 100% saturation. Atomistic molecular dynamic simulations show the impact is driven by an anti-polyelectrolyte effect from zwitterionic polymers. Uncharged polymers exhibit polymer length-dependent decreased solubility. The differences in salting-out are then used to simply purify mixtures of conjugates and native proteins into single species. Increasing protein solubility in salt solutions through polymer conjugation could lead to many new applications of protein-polymer conjugates.

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“…Finally, the use of biomolecules in the development of materials is garnering increased interest. 7 The modification of an amino acid greatly expands its utility in chemical synthesis. Many synthetic strategies rely on naturally occurring chirality to control the stereoselectivity of Thomas A.…”

Section: Introductionmentioning

confidence: 99%

Photocatalytic methods for amino acid modification

et al. 2021

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Next generation protein‐polymer conjugates

Abstract: Structure-function-dynamics relationships are the foundation from which we will expand the impact of protein-polymer conjugates by understanding how specific protein-polymer

Cited by 75 publications

References 153 publications

Insight into Protein–Polymer Conjugate Relaxation Dynamics: The Importance of Polymer Grafting

Insight into Protein–Polymer Conjugate Relaxation Dynamics: The Importance of Polymer Grafting

Transforming protein-polymer conjugate purification by tuning protein solubility

Photocatalytic methods for amino acid modification

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