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TechNote - Researchers PEG solution to prolong in vivo effect of MMP inhibitor

Excess of matrix metalloproteinases (MMPs) activity has long been linked with the development and progression of several pathologies including cardiovascular diseases, arthritis and cancer. Their activities are regulated by a family of protease inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), which have been reported to reduce tumor growth and metastasis in several cancer models, and are regarded as promising anti-cancer therapies. However, the use of proteins and peptides as potential biopharmaceuticals are often restricted by their short half-life in biological fluids and their rapid renal clearance once administered in vivo. PEGylation, the covalent conjugation of polyethylene glycol chains to a protein, represents a means to counteract these effects and is now widely used as a post-production chemical modification for improving biomedical efficacy and physico-chemical properties of therapeutic proteins. In their publication in PLoS One, Dr. Batra and co-workers from the Department of Cancer Biology at the Mayo Clinic Cancer Center showed the benefits of PEGylation of recombinant human TIMP-1 in vitro and in vivo. The authors reported several different strategies for the expression, purification and modification of PEGylated rhTIMP-1. This modification contributed significantly to the extension of this protein’s half-life in murine plasma, the full preservation of its MMP inhibitory activity in vitro and an improved inhibitory potency in vivo. These results highlight the benefits of PEGylation as an attractive strategy to improve the pharmacokinetic profile of TIMPs without interfering with their intended therapeutic effect.

Enzo’s PEGylated protein ELISA kit offers an easy and efficient way to measure and quantify PEGylated molecules in a variety of sample types. Enzo Life Sciences also has a comprehensive portfolio for bioprocess and biotherapeutics development including protein aggregation and thermal shift stability kits, live cell analysis kits, gene expression analysis assays, antibodies and biochemicals; some of which are described below:

 

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References:

  • Batra J, et al. PEGylation extends circulation half-life while preserving in vitro and in vivo activity of tissue inhibitor of metalloproteinases-1 (TIMP-1). PLoS One. (2012) 7: e50028..

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