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Fibroblast growth factor-21 (FGF21) signaling requires the presence of beta-Klotho, a co-receptor with a very short cytoplasmic domain. Here we show that FGF21 binds directly to beta-Klotho through its C-terminus. Serial C-terminal truncations of FGF21 weakened or even abrogated its interaction with beta-Klotho in a Biacore assay, and led to gradual loss of(More)
Fibroblast growth factor 21 (FGF21) is a promising drug candidate for the treatment of type 2 diabetes. However, the use of wild type native FGF21 is challenging due to several limitations. Among these are its short half-life, its susceptibility to in vivo proteolytic degradation and its propensity to in vitro aggregation. We here describe a rationale-based(More)
The pfk gene encoding phosphofructokinase (Pfk) from the anaerobic bacterium Clostridium acetobutylicum ATCC 824 was cloned and sequenced. The gene was identified in a plasmid library by complementation of an E. coli pfk mutant and by the ability to amplify a fragment by PCR using primers based on homologous regions of Pfk from other microorganisms.(More)
Fibroblast growth factor 21 (FGF21) is involved in regulating energy metabolism, and it has shown significant promise as a treatment for type II diabetes; however, the native protein has a very short circulating half-life necessitating frequent injections to maintain a physiological effect. Polyethylene glycol (PEG) conjugation to proteins has been used as(More)
Fibroblast growth factor 21 (FGF21) has potent effects on normalizing glucose, lipid, and energy homeostasis, and represents an attractive novel therapy for type 2 diabetes mellitus and obesity. Approaches to improve the pharmacokinetic properties of FGF21, such as conjugation with polyethylene glycol, have been explored for therapeutic development.(More)
High levels of translational errors, both truncation and misincorporation in an Fc-fusion protein were observed. Here, we demonstrate the impact of several commercially available codon optimization services, and compare to a targeted strategy. Using the targeted strategy, only codons known to have translational errors are modified. For an Fc-fusion protein(More)
The Clostridium acetobutylicum ATCC 824 DNA containing the 3′ end of a PriA homolog, deformylase (def), and the 5′ end of formyltransferase (fmt) has been cloned, sequenced, and used to complement an Escherichia coli mutant. While def and fmt have been found sharing an operon in other organisms, the presence of a third gene within a putative operon has not(More)
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