Mosquito-Derived Anophelin Sulfoproteins Are Potent Antithrombotics.
Emma E Watson, Xuyu Liu, Robert E Thompson, Jorge Ripoll-Rozada, Mike Wu, Imala Alwis, Alessandro Gori, Choy-Theng Loh, Benjamin L Parker, Gottfried Otting, Shaun Jackson, Pedro José Barbosa Pereira, Richard J Payne
ACS Central Science | Published : 2018
The anophelins are small protein thrombin inhibitors that are produced in the salivary glands of the Anopheles mosquito to fulfill a vital role in blood feeding. A bioinformatic analysis of anophelin sequences revealed the presence of conserved tyrosine residues in an acidic environment that were predicted to be post-translationally sulfated in vivo. To test this prediction, insect cell expression of two anophelin proteins, from Anopheles albimanus and Anopheles gambiae, was performed, followed by analysis by mass spectrometry, which showed heterogeneous sulfation at the predicted sites. Homogeneously sulfated variants of the two proteins were subsequently generated by chemical synthesis via..View full abstract