Site-specific PEGylation of proteins by a Staudinger-phosphite reaction

Serwa, Remigiusz A.; Majkut, Paul; Horstmann, Benjamin; Swiecicki, Jean-Marie; Gerrits, Michael; Krause, Eberhard; Hackenberger, Christian P. R.

doi:10.1039/c0sc00324g

Cited by 80 publications

(50 citation statements)

References 61 publications

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“…9,10 This effect may be eliminated in poly(zwitterion)-based conjugates. 4 Furthermore, reversible PEGylation strategies have been developed that take advantage of slowly hydrolysable, 12,13 light-sensitive 14 or thiol-sensitive 15 linkers to release the PEG component.…”

Section: Introductionmentioning

confidence: 99%

Noncovalent PEGylation via Lectin–Glycopolymer Interactions

et al. 2016

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The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 2 AbstractPEGylation, the covalent modification of proteins with polyethylene glycol, is an abundantly used technique to improve the pharmacokinetics of therapeutic proteins. The drawback with this methodology is that the covalently attached PEG can impede the biological activity (e.g. reduced receptor-binding capacity). Protein therapeutics with "disposable" PEG modifiers have potential advantages over the current technology. Here, we show that a protein-polymer "Medusa complex" is formed by the combination of a hexavalent lectin with a glycopolymer. Using NMR spectroscopy, small angle X-ray scattering (SAXS), size exclusion chromatography and native gel electrophoresis it was demonstrated that the fucose-binding lectin RSL and a fucose-capped polyethylene glycol (Fuc-PEG) form a multimeric assembly. All of the experimental methods provided evidence of noncovalent PEGylation with a concomitant increase in molecular mass and hydrodynamic radius. The affinity of the protein-polymer complex was determined by ITCand competition experiments to be in the µM range, suggesting that such systems have potential biomedical applications.

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Section: Introductionmentioning

confidence: 99%

Noncovalent PEGylation via Lectin–Glycopolymer Interactions

et al. 2016

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“…41 Furthermore, P(O)─Cl bond formation has also been investigated via Michaelis-Arbuzov rearrangement of trialkyl phosphite with Cl 2 . [47][48][49][50] This synthesis procedure involves the reaction of alkyl azides with trialkyl phosphite to produce phosphorimidates, followed by rearrangement to their corresponding phosphoramidates. However, upscaling of these synthetic procedures is challenging because of their exothermic nature, expensive raw material as well as side products and moderate reactions yields.…”

Section: General Synthesis Methodsmentioning

confidence: 99%

Recent developments in P(O/S)–N containing flame retardants

Nazir

Gaan

2019

J of Applied Polymer Sci

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Synthesis of organophosphorus compounds containing nitrogen as heteroatom and its application as a flame retardant (FR) have attracted much attention in the academic and industrial communities over the past decade. Such compounds are relatively easy to synthesize and offer advantages such as high thermal stability, which is useful for high temperature processing, improved char stability, density, and yield during the thermal decomposition of polymer, and release phosphorus species active in the flame inhibition process. Though a variety of phosphorus-nitrogen (P-N) compounds can be found in the literature, this review mostly summarizes the recent (since 2013) development in phosphorus (O)-nitrogen containing flame retardants which have been published in peer-reviewed journals. General strategies of synthesizing P(O)-N compounds as FRs from various phosphorus-based starting materials are highlighted in this review. Some of the most common classes of researched P(O)-N containing compounds as FRs include the phosphinamides, phosphonamides, phosphoramides, phosphoramidates, phosphorodiamidates, phosphonamidates and their thio counterparts which are usually obtained via a one-or two-step synthetic strategy. Incorporation of these compounds as FRs in various polymer systems such as polyurethane, epoxy resins, polyamides, cellulose, polylactide, poly(butylene terephthalate), polycarbonates, and acrylonitrile-butadiene-styrene are discussed in detail in this review. Special emphasis on the various fire and thermal performances of the new materials are also summarized. The mechanical performance of new materials and the influence of these additives on polymer processing are also briefly discussed.

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“…103 This strategy is called Staudinger ligation and has been widely applied to living animal cell labelling, 104 protein labelling, 105,106 and protein immobilization. 109 A symmetrical phosphite enables the introduction of two functional moieties into one conjugation site. In the Staudinger-phosphite reaction, azide react with phosphite instead of phosphane, resulting in the formation of phosphoramidate.…”

Section: Staudinger Ligationmentioning

confidence: 99%

“…107 Recently, as a modified Staudinger ligation, the Staudinger-phosphite reaction was developed. 109 When a light-cleavable phosphite reacted with an azide in a protein, it rendered protein phosphorylation 108 or lightdegradable PEG. 108 The Staudinger-phosphite reaction was successfully used for protein conjugation in E. coli lysates.…”

Section: Staudinger Ligationmentioning

confidence: 99%

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Expansion of bioorthogonal chemistries towards site-specific polymer–protein conjugation

Jung

Kwon

2016

Polym. Chem.

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Polymer conjugation to proteins has been widely used to improve or expand protein properties. However, polymer conjugation to random sites of a target protein often led to a significant loss of critical protein properties. In order to overcome this, polymer conjugation to specific sites of a protein was developed using the site-specific introduction of non-natural amino acids and bioorthogonal chemistries. This review summarizes the recent advances in bioorthogonal chemistries. As the repertoire of bioorthogonal chemistries available for polymer conjugation is expanding, the site-specific polymer conjugation technique would be a valuable platform technique to design novel protein-polymer conjugates.

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Site-specific PEGylation of proteins by a Staudinger-phosphite reaction

Cited by 80 publications

References 61 publications

Noncovalent PEGylation via Lectin–Glycopolymer Interactions

Noncovalent PEGylation via Lectin–Glycopolymer Interactions

Recent developments in P(O/S)–N containing flame retardants

Expansion of bioorthogonal chemistries towards site-specific polymer–protein conjugation

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