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Half-Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation

van Witteloostuijn, Søren B. ; Pedersen, Søren L. ; Jensen, Knud J.

ChemMedChem, 2016-11, Vol.11 (22), p.2474-2495 [Revista revisada por pares]

Germany: Blackwell Publishing Ltd

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  • Título:
    Half-Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation
  • Autor: van Witteloostuijn, Søren B. ; Pedersen, Søren L. ; Jensen, Knud J.
  • Materias: Alternatives ; Biological Products - chemistry ; Biological Products - metabolism ; biopharmaceuticals ; drug delivery ; Half-Life ; half-life extension ; Humans ; Molecular Structure ; peptides ; Peptides - chemistry ; Peptides - metabolism ; Polyethylene Glycols - chemistry ; proteins ; Proteins - chemistry ; Proteins - metabolism
  • Es parte de: ChemMedChem, 2016-11, Vol.11 (22), p.2474-2495
  • Notas: istex:E0F6C13F56FB9EF413C9FD283AD70419A94D007B
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    ObjectType-Review-1
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  • Descripción: Peptides and proteins constitute a vast pool of excellent drug candidates. Evolution has equipped these molecules with superior drug‐like properties such as high specificity and potency. However, native peptides and proteins suffer from an inadequate pharmacokinetic profile, and their outstanding pharmacological potential can only be realized if this issue is addressed during drug development. To overcome this challenge, a variety of half‐life extension techniques relying on covalent chemical modification have been developed. These methods include PEGylation, fusion to unstructured polypeptide‐based PEG mimetics, conjugation of large polysaccharides, native‐like glycosylation, lipidation, fusion to albumin or the Fc domain of IgG, and derivatization with bio‐orthogonal moieties that direct self‐assembly. This review provides an overview of available conjugation chemistries, biophysical properties, and safety data associated with these concepts. Moreover, the effects of these modifications on peptide and protein pharmacokinetics are demonstrated through key examples. An alternative direction: Despite the commercial success of PEGylation, new strategies for extending the half‐lives of biopharmaceuticals are warranted. In this review, we describe the available alternatives with an emphasis on conjugation chemistry, biophysical properties, and biological compatibility.
  • Editor: Germany: Blackwell Publishing Ltd
  • Idioma: Inglés;Alemán
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