Enhancement of therapeutic protein in vivo activities through glycoengineering

@article{Elliott2003EnhancementOT,
  title={Enhancement of therapeutic protein in vivo activities through glycoengineering},
  author={Steven G. Elliott and Tony Lorenzini and Sheilah J. Asher and Kenneth H. Aoki and David W. Brankow and Lynette Buck and Leigh A. Busse and David Chang and Janis Fuller and James Grant and Natasha Hernday and Martha Hokum and Sylvia Hu and Andrew Knudten and Nancy J Levin and Renee Komorowski and F Bachmann Martin and Rachell Navarro and Timothy D. Osslund and Gary Rogers and Norma Rogers and Geri Trail and Joan C. Egrie},
  journal={Nature Biotechnology},
  year={2003},
  volume={21},
  pages={414-421}
}
Delivery of protein therapeutics often requires frequent injections because of low activity or rapid clearance, thereby placing a burden on patients and caregivers. Using glycoengineering, we have increased and prolonged the activity of proteins, thus allowing reduced frequency of administration. Glycosylation analogs with new N-linked glycosylation consensus sequences introduced into the protein were screened for the presence of additional N-linked carbohydrates and retention of in vitro… 
Glycoengineering: the effect of glycosylation on the properties of therapeutic proteins.
TLDR
The discovery of darbepoetin alfa (DA), a hyperglycosylated analogue of erythropoietin that contains two additional N-linked carbohydrates, a threefold increase in serum half-life and increased in vivo activity compared to recombinant human ery Anthropo-EPO, is discussed.
Glycosylation of Therapeutic Proteins
TLDR
An account of the effects that glycosylation has on the therapeutic efficacy of protein drugs is provided and the current understanding of the mechanisms by which glyCosylation leads to such effects are described.
Therapeutic proteins: Glycoengineered to last longer
  • S. Farley
  • Biology
    Nature Reviews Drug Discovery
  • 2003
TLDR
This success, and further experiments reported by Elliott and colleagues showing that glycosylation analogues of leptin and Mpl ligand also had increased in vivo activity and duration of action, indicates that glycoengineering could be a generally applicable strategy for improving therapeutic proteins.
Optimization of physicochemical and pharmacological properties of peptide drugs by glycosylation.
TLDR
Various synthetic approaches to prepare N- and O-glycopeptides bearing simple monosaccharides as a tool to improve peptide therapeutic efficacy by glycosylation are described.
Chemical (neo)glycosylation of biological drugs.
Glycosylated enfuvirtide: a long-lasting glycopeptide with potent anti-HIV activity.
TLDR
It is reported here that the pharmacokinetics of an anti-HIV peptide drug enfuvirtide (ENF) can be dramatically improved by a chemical glycosylation approach, and this approach may be useful for the development of novel protein and peptide drugs with enhanced pharmaceutical properties.
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