Contemporary Approaches for Site‐Selective Dual Functionalization of Proteins

Xu, Lujuan; Kuan, Seah Ling; Weil, Tanja

doi:10.1002/anie.202012034

Cited by 62 publications

(61 citation statements)

References 156 publications

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“…Overall, these results confirm a striking chemoselectivity and mutual orthogonality between both methods and indicate that both cycloadditions share similar kinetic profiles under these conditions. This mutual orthogonality promises relevant applications, such as for the dual tagging of biomolecules [22] …”

Section: Resultsmentioning

confidence: 98%

Bioorthogonal Azide–Thioalkyne Cycloaddition Catalyzed by Photoactivatable Ruthenium(II) Complexes

et al. 2021

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Tailored ruthenium sandwich complexes bearing photoresponsive arene ligands can efficiently promote azide–thioalkyne cycloaddition (RuAtAC) when irradiated with UV light. The reactions can be performed in a bioorthogonal manner in aqueous mixtures containing biological components. The strategy can also be applied for the selective modification of biopolymers, such as DNA or peptides. Importantly, this ruthenium‐based technology and the standard copper‐catalyzed azide–alkyne cycloaddition (CuAAC) proved to be compatible and mutually orthogonal.

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Section: Resultsmentioning

confidence: 98%

Bioorthogonal Azide–Thioalkyne Cycloaddition Catalyzed by Photoactivatable Ruthenium(II) Complexes

et al. 2021

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“…Bioorthogonal reactions rely on introduction into the polymers of functional groups different from those found in amino acid side chains, able to chemoselectively react in mild conditions with high yields. Among them, the so-called click chemistry [24][25][26][27], based, for example, on Huisgen-type cycloaddition [28], Staudinger reaction [29,30], Diels-Alder [31][32][33], thiol-ene addition [34,35], and carbonyl/oxime-hydrazone chemistry [36,37], has been proposed over recent years. The main drawback of bioorthogonal reactions arises from the need for a two-step process, involving first the introduction of orthogonal functional groups, either by chemical or enzymatic reactions [38] or protein engineering [39] approaches.…”

Section: Introductionmentioning

confidence: 99%

Photoinduced Porcine Gelatin Cross-Linking by Homobi- and Homotrifunctional Tetrazoles

Vaghi

Monti

Marelli³

et al. 2021

Gels

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Gelatin is a costless polypeptide material of natural origin, able to form hydrogels that are potentially useful in biomaterial scaffold design for drug delivery, cell cultures, and tissue engineering. However, gelatin hydrogels are unstable at physiological conditions, losing their features only after a few minutes at 37 °C. Accordingly, treatments to address this issue are of great interest. In the present work, we propose for the first time the use of bi- and trifunctional tetrazoles, most of them unknown to date, for photoinduced gelatin cross-linking towards the production of physiologically stable hydrogels. Indeed, after UV-B irradiation, aryl tetrazoles generate a nitrilimine intermediate that is reactive towards different functionalities, some of them constitutively present in the amino acid side chains of gelatin. The efficacy of the treatment strictly depends on the structure of the cross-linking agent used, and substantial improved stability was observed by switching from bifunctional to trifunctional cross-linkers.

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“…It is commonly agreed that these tools will provide major insight into basic biology and enable the development of functional bioconjugates with unprecedented properties. To deliver on these promises, it will be key to discover new technologies that offer not only bioconjugation efficacy, but as importantly, site‐selectivity, orthogonality and new mechanisms to control the peptide structure [2] …”

Section: Introductionmentioning

confidence: 99%

Efficient Amino‐Sulfhydryl Stapling on Peptides and Proteins Using Bifunctional NHS‐Activated Acrylamides

et al. 2021

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Widely used reagents in the peptide functionalization toolbox, Michael acceptors and N‐hydroxysuccinimide (NHS) activated esters, are combined in NHS‐activated acrylamides for efficient chemoselective amino‐sulfhydryl stapling on native peptides and proteins. NHS‐activated acrylamides allow for a fast functionalization of N‐terminal cysteines (k2=1.54±0.18×103 M−1 s−1) under dilute aqueous conditions, enabling selectivity over other nucleophilic amino acids. Additionally, the versatility of these new bioconjugation handles was demonstrated in the cross‐linking of in‐chain or C‐terminal cysteines with nearby lysine residues. NHS‐activated acrylamides are compatible with the use of other cysteine selective reagents, allowing for orthogonal dual‐modifications. This strategy was successfully applied to the late‐stage functionalization of peptides and proteins with a PEG unit, fluorescent probe, and cytotoxic agent. The level of molecular control offered by NHS‐activated acrylamides is expected to promote amino‐sulfhydryl stapling technology as a powerful strategy to design functional bioconjugates.

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Contemporary Approaches for Site‐Selective Dual Functionalization of Proteins

Cited by 62 publications

References 156 publications

Bioorthogonal Azide–Thioalkyne Cycloaddition Catalyzed by Photoactivatable Ruthenium(II) Complexes

Bioorthogonal Azide–Thioalkyne Cycloaddition Catalyzed by Photoactivatable Ruthenium(II) Complexes

Photoinduced Porcine Gelatin Cross-Linking by Homobi- and Homotrifunctional Tetrazoles

Efficient Amino‐Sulfhydryl Stapling on Peptides and Proteins Using Bifunctional NHS‐Activated Acrylamides

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