One-Step Protein–Polymer Conjugates from Boronic-Acid-Functionalized Polymers

Swierczynski, Michael J.; Ball, Zachary T.

doi:10.1021/acs.bioconjchem.0c00516

Cited by 9 publications

(7 citation statements)

References 38 publications

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“…This simple and efficient cysteine arylation paves the way for the synthesis of more complex biopolymer structures and architectures. A combination of boronic acid cross coupling and S N Ar cyclization proved effective for preparing stapled peptide structures (Figure 5c), [38] and boronic macromolecular reagents could be used to directly prepare protein‐polymer conjugates (Figure 5d) [43] …”

Section: Discussionmentioning

confidence: 99%

Boronic Acid Reagents for Transition‐Metal‐Mediated Cross‐Coupling with Proteins and Peptides

Miller

Ball

2021

Israel Journal of Chemistry

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Transition‐metal catalysis provides new approaches to selectivity and the activation of otherwise inert functional groups. Bioconjugation with protein and peptide substrates presents numerous challenges of functional group activation and selectivity, and transitional‐metal approaches provide important alternative solutions to these challenges. This article describes the development of boronic acid reagents for new selective approaches to modification of peptides and proteins, focusing primarily on catalytic C−X bond formation.

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Section: Discussionmentioning

confidence: 99%

Boronic Acid Reagents for Transition‐Metal‐Mediated Cross‐Coupling with Proteins and Peptides

Miller

Ball

2021

Israel Journal of Chemistry

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“…67,74 This approach was used to produce GFP and T4 lysozyme homodimers with conversions of approximately 50%. 74 In addition, Cu(II)-catalyzed, histidine directed, backbone N−H arylation and alkenylation of proteins with boronic acids was achieved. 75 By sequential addition of a heterobifunctional linker featuring 2-nitro-arylboronic acid and (E)-alkenylboronic acid functionalities, orthogonal Ni(II)promoted cysteine arylation followed by Cu(II)-catalyzed histidine-directed backbone N−H alkenylation was achieved.…”

Section: Targeting Canonical Amino Acidsmentioning

confidence: 99%

“…In addition to Pd-mediated conjugation, proteins were also conjugated via cysteine arylation chemistry using bis-arylboronic acid homobifunctional polymers and a Ni(II) catalyst. , This approach was used to produce GFP and T4 lysozyme homodimers with conversions of approximately 50% . In addition, Cu(II)-catalyzed, histidine directed, backbone N–H arylation and alkenylation of proteins with boronic acids was achieved .…”

Section: Targeting Canonical Amino Acidsmentioning

confidence: 99%

Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation

et al. 2022

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Fusion proteins play an essential role in the biosciences but suffer from several key limitations, including the requirement for N-to-C terminal ligation, incompatibility of constituent domains, incorrect folding, and loss of biological activity. This perspective focuses on chemical and enzymatic approaches for the post-translational generation of well-defined protein−protein conjugates, which overcome some of the limitations faced by traditional fusion techniques. Methods discussed range from chemical modification of nucleophilic canonical amino acid residues to incorporation of unnatural amino acid residues and a range of enzymatic methods, including sortase-mediated ligation. Through summarizing the progress in this rapidly growing field, the key successes and challenges associated with using chemical and enzymatic approaches are highlighted and areas requiring further development are discussed.

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“…Additionally, elevated reaction temperatures are occasionally employed to achieve near quantitative conversion, which can be detrimental to the structure and function of more delicate biomolecules. 9,15,16 In an attempt to overcome some of these challenges, bioconjugation strategies have been developed utilizing noncanonical amino acids with more traditional "click" reactivity, notably alkynes with azides, to achieve faster rates. 10,17 However, these non-natural modifications require challenging protein expression techniques and can also perturb the natural structure and activity of the biomolecule.…”

Section: ■ Introductionmentioning

confidence: 99%

Organometallic S-arylation Reagents for Rapid PEGylation of Biomolecules

Montgomery¹,

Messina²,

Doud³

et al. 2022

Bioconjugate Chem.

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Bioconjugation techniques for biomolecule–polymer conjugation are numerous; however, slow kinetics and steric challenges generally necessitate excess reagents or long reaction times. Organometallic transformations are known to circumvent these issues; yet, harsh reaction conditions, incompatibility in aqueous media, and substrate promiscuity often limit their use in a biological context. The work reported herein demonstrates a facile and benign organometallic Au(III) S-arylation approach that enables the synthesis of poly(ethylene glycol) monomethyl ether (mPEG)-protein conjugates with high efficiency. Isolable and bench-stable 2, 5, and 10 kDa mPEG-Au(III) reagents were synthesized via oxidative addition into terminal aryl iodide substituents installed on mPEG substrates with a (Me-DalPhos)Au(I)Cl precursor. Reaction of the isolable mPEG-Au(III) oxidative addition complexes with a cysteine thiol on a biomolecule resulted in facile and selective cysteine arylation chemistry, forging covalent S-aryl linkages and affording the mPEG-biomolecule conjugates. Notably, low polymer reagent loadings were used to achieve near quantitative conversion at room temperature in 1 min due to the rapid kinetics and high chemoselectivity of this Au-based bioconjugation approach. Therefore, this work represents an important addition to the protein–polymer conjugation chemical toolbox.

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One-Step Protein–Polymer Conjugates from Boronic-Acid-Functionalized Polymers

Cited by 9 publications

References 38 publications

Boronic Acid Reagents for Transition‐Metal‐Mediated Cross‐Coupling with Proteins and Peptides

Boronic Acid Reagents for Transition‐Metal‐Mediated Cross‐Coupling with Proteins and Peptides

Chemical and Enzymatic Methods for Post-Translational Protein–Protein Conjugation

Organometallic S-arylation Reagents for Rapid PEGylation of Biomolecules

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