Multivalent and Flexible PEG-Nitrilotriacetic Acid Derivatives for Non-covalent Protein Pegylation

Mero, Anna; Ishino, Tetsuya; Chaiken, Irwin M.; Veronese, Francesco M.; Pasut, Gianfranco

doi:10.1007/s11095-011-0468-8

Cited by 33 publications

(40 citation statements)

References 26 publications

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“…[16][17][18][19][20][21][22][23][24][25][26] Examples include polymer conjugation via: co-factor reconstitution, 16 the biotin-streptavidin complex, 18 supramolecular complexation with cucurbituril, 19 charge-charge 20 and metal affinity 21,24 interactions, as well as lectin-mediated complexation. 25,27,28 The advantage of noncovalent systems is that temporal control of conjugate assembly and disassembly can be asserted by the presence of competitor molecules.…”

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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“…2). A PEG-nitrilotriacetic acid showed a great affinity with native proteins such as G-CSF and hemoglobin possessing a discrete number of histidine in the sequence [63]. It is unknown, as far as these approaches are concerned, if or how long the PEG / protein interaction is maintained in vivo after the complex has reached the blood stream and if the protein is displaced by competition with other proteins.…”

Section: Figurementioning

confidence: 99%

“…Example of a PEG-nitrilotriacetic acid derivative for IMAC based complex formation with proteins (adapted from [63]). …”

Section: Figurementioning

confidence: 99%

Drug and protein delivery by polymer conjugation

Grigoletto

Maso

Mero

et al. 2016

Journal of Drug Delivery Science and Technology

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“…Metal ions can bind histidine residues of proteins, a phenomenon referred to as metal-chelate affinity. This type of binding is applied to other principles of noncovalent PEGylation between protein and PEG derivatives: PEGylated nitrilotriacetic acid with Cu 2+ metal ions bound to hemoglobin, human growth hormone, interferon, insulin, and granulocyte colony stimulating factor [83].…”

Section: Stabilization Of Protein By Pegylated Polymermentioning

confidence: 99%