AI Article Synopsis
- FGF21 is a hormone with potential for treating metabolic diseases like type 2 diabetes and obesity, but its use as a therapy has been limited due to instability and breakdown in the body.
- Researchers created modified versions of FGF21 by adding cysteine residues and using a PEGylation technique to improve its stability and longevity in the bloodstream.
- The modified FGF21 not only maintained its biological activity but also significantly increased its half-life, suggesting a new method to enhance the effectiveness of protein-based drugs.
Article Abstract
Fibroblast growth factor 21 (FGF21) is an endocrine-acting hormone that has the potential to treat metabolic diseases, such as type 2 diabetes and obesity. Development of FGF21 into a therapeutic has been hindered due to its low intrinsic bio-stability, propensity towards aggregation and its susceptibility to in vivo proteolytic degradation. In order to address these shortcomings, we've developed recombinant human FGF21 variants by strategically introducing cysteine residues via site-directed mutagenesis, and have also developed a solid-phase nickel affinity PEGylation strategy, whereby engineered, surface-exposed cysteine residues of immobilized proteins were used as a platform to efficiently and site-selectively conjugate with PEG-maleimide. The engineered PEGylated FGF21 conjugates retained its biological functions, as well as demonstrated an increase in half-life by over 211.3 min. By demonstrating the biological activity of the FGF21 analog as a prototype, we have also provided a "generalized" solid-phase approach to effectively increase serum half-life of protein therapeutics.
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| http://dx.doi.org/10.1016/j.biomaterials.2014.03.023 | DOI Listing |
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