Structural characterization of PEGylated rHuG-CSF and location of PEG attachment sites

Cindrić, Mario; Čepo, Tina; Galić, Nives; Bukvić-Krajačić, Mirjana; Tomczyk, Nick; Vissers, Johaness P.C.; Bîndilă, Laura; Peter‐Katalinić, Jasna

doi:10.1016/j.jpba.2007.02.036

Cited by 37 publications

(23 citation statements)

References 30 publications

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“…However despite the resulting two molecules having very different potencies and pharmacokinetics they display very similar clinical efficacy. Another example is MICERA ® (Roche, Switzerland), which is epoetin-beta that has been conjugated to a 30 kDa PEG through an amide bond to either the N-terminal amino group or the ɛ-amino group of lysine and was approved in Europe in 2007 for the treatment of anemia associated with chronic kidney disease [32,[82][83][84][85][86][87][88][89][90][91][92][93].…”

Section: Future Science Groupmentioning

confidence: 99%

Pegylation and Its Impact on the Design of New Protein-Based Medicines

Ginn¹,

Khalili²,

Lever³

et al. 2014

Future Med. Chem.

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PEGylation is the covalent conjugation of PEG to therapeutic molecules. Protein PEGylation is a clinically proven approach for extending the circulation half-life and reducing the immunogenicity of protein therapeutics. Most clinically used PEGylated proteins are heterogeneous mixtures of PEG positional isomers conjugated to different residues on the protein main chain. Current research is focused to reduce product heterogeneity and to preserve bioactivity. Recent advances and possible future directions in PEGylation are described in this review. So far protein PEGylation has yielded more than 10 marketed products and in view of the lack of equally successful alternatives to extend the circulation half-life of proteins, PEGylation will still play a major role in drug delivery for many years to come.

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Section: Future Science Groupmentioning

confidence: 99%

Pegylation and Its Impact on the Design of New Protein-Based Medicines

Ginn¹,

Khalili²,

Lever³

et al. 2014

Future Med. Chem.

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“…21) We previously described the preparation of mono-PEGylated rhG-CSF using trimeric-structured mPEG-NHS 16) and the structural characterization of individual positional isomers isolated from mono-PEGylated rhG-CSF using a preparative two-step chromatography method developed. The Lys 35 , Met N-terminal , Lys…”

mentioning

confidence: 99%

<i>In Vivo</i> Pharmacokinetics and Pharmacodynamics of Positional Isomers of Mono-PEGylated Recombinant Human Granulocyte Colony Stimulating Factor in Rats

Kang

Lee

2013

Biological & Pharmaceutical Bulletin

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Key words random PEGylation; covalent conjugation; individual positional isomer; in vitro biological activity; blood half-life PEGylation describes the chemical modification of therapeutic proteins by covalent conjugation with polyethylene glycol (PEG), a non-toxic, non-immunogenic polymer that is approved by U.S. Food and Drug Administration (FDA) for parental administration, that is used as a strategy to overcome the disadvantages associated with therapeutic proteins with a short half-life due to rapid clearance from the body.

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“…Reductive amination has been extensively investigated for protein N-terminal conjugation [165,[169][170][171], and this process is used for pegfilgrastim (PEG-G-CSF). Imine formation is the first step in reductive amination with water as the byproduct, and so homogeneous imine formation is not generally efficient in terms of reagent stoichiometry or site specificity [170,172]. Efforts have been published to optimize reductive amination to G-CSF [173] and other proteins (e.g.…”

Section: Protein Pegylationmentioning

confidence: 99%

Chemical and Genetic Modification

Farys¹,

Ginn²,

Badescu³

et al. 2013

Pharmaceutical Sciences Encyclopedia

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There are many natural post‐translational modifications of proteins (e.g., glycosylation, ubiquitination, acylation,and amino acid derivatization).Glycosylation is common for therapeutic proteins. Classes of proteins modified by glycosylation include monoclonal antibodies, blood factors, hematopoietic proteins, and cytokines. Excluding monoclonal antibodies, many proteins were, at least when they were first introduced to the clinic, designed to be used as a replacement protein for the corresponding endogenous protein. Maintaining control of the protein structure to be as close as possible to the structure of the endogeneous protein is therefore a key goal. In this review, we focus on (i) optimization of protein pharmacokinetics, (ii) improvement of protein properties to be used as medicines (this primarily includes reduction of immunogenic sequences and improvement of protein stability), (iii) addition of a therapeutic effect, and (iv) use of proteins as diagnostics.

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Structural characterization of PEGylated rHuG-CSF and location of PEG attachment sites

Cited by 37 publications

References 30 publications

Pegylation and Its Impact on the Design of New Protein-Based Medicines

Pegylation and Its Impact on the Design of New Protein-Based Medicines

<i>In Vivo</i> Pharmacokinetics and Pharmacodynamics of Positional Isomers of Mono-PEGylated Recombinant Human Granulocyte Colony Stimulating Factor in Rats

Chemical and Genetic Modification

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