Blood-feeding arthropods (such as ticks, mosquitoes and leeches) produce potent anti-coagulant proteins in their saliva to facilitate access to their blood meal. These compounds interfere with the coagulation cascade - a series of enzymes which regulate the process of blood clotting - particularly targeting the central enzyme of the cascade thrombin. Undesired blood clotting is implicated in several serious human diseases, including deep vein thrombosis and stroke, with thrombin inhibition representing a common therapeutic target.¹ Using a bioinformatic approach, we have identified several proteins from blood-feeding organisms (including mosquitoes² and ticks³) which not only possess potent thrombin inhibitory activity but which are modulated by post-translational tyrosine sulfation. Through a rapid, ligation-based platform we have gained access to a library of tick- and mosquito-derived sulfoproteins enabling us to probe the natural variance in potency amongst homologous proteins in a manner akin to small molecule medicinal chemistry. In this way we hope to exploit the innate anti-coagulant activities of these proteins and expedite their translation to elucidate pre-clinical anticoagulant leads.

1. Lee, C. J. and Ansell, J. E. Direct thrombin inhibitors. British journal of clinical pharmacology 72, 581-592, (2011).
2. Watson, E. E. et al. Mosquito derived Anophelin sulfoproteins are potent antithrombotics. ACS central science, 4, 468-476 (2018).
3. Watson, E. E. et al. Rapid assembly and profiling of an anticoagulant sulfoprotein library. Proceedings of the National Academy of Sciences U.S.A., (doi:10.1073/pnas.1905177116).