Chemical Synthesis of the Highly Hydrophobic Antiviral Membrane-Associated Protein IFITM3 and Modified Variants.
Thibault J HarmandVijaya R PattabiramanJeffrey W BodePublished in: Angewandte Chemie (International ed. in English) (2017)
Interferon-induced transmembrane protein 3 (IFITM3) is an antiviral transmembrane protein that is thought to serve as the primary factor for inhibiting the replication of a large number of viruses, including West Nile virus, Dengue virus, Ebola virus, and Zika virus. Production of this 14.5 kDa, 133-residue transmembrane protein, especially with essential posttranslational modifications, by recombinant expression is challenging. In this report, we document the chemical synthesis of IFTIM3 in multi-milligram quantities (>15 mg) and the preparation of phosphorylated and fluorescent variants. The synthesis was accomplished by using KAHA ligations, which operate under acidic aqueous/organic mixtures that excel at solubilizing even the exceptionally hydrophobic C-terminal region of IFITM3. The synthetic material is readily incorporated into model vesicles and forms the basis for using synthetic, homogenous IFITM3 and its derivatives for further studying its structure and biological mode of action.
Keyphrases
- simultaneous determination
- zika virus
- dengue virus
- ionic liquid
- aedes aegypti
- amino acid
- binding protein
- protein protein
- copy number
- poor prognosis
- quantum dots
- gene expression
- dendritic cells
- signaling pathway
- dna methylation
- long non coding rna
- endothelial cells
- mass spectrometry
- heat shock protein
- oxidative stress
- molecularly imprinted
- structure activity relationship