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Mosquito-Derived Anophelin Sulfoproteins Are Potent Antithrombotics.

ABSTRACT: 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 a one-pot ligation-desulfurization strategy. Tyrosine sulfation of the anophelins was shown to significantly enhance the thrombin inhibitory activity, with a doubly sulfated variant of the anophelin from A. albimanus exhibiting a 100-fold increase in potency compared with the unmodified homologue. Sulfated anophelins were also shown to exhibit potent in vivo anticoagulant and antithrombotic activity.

SUBMITTER: Watson EE

PROVIDER: S-EPMC5920608 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Mosquito-Derived Anophelin Sulfoproteins Are Potent Antithrombotics.

Watson Emma E EE Liu Xuyu X Thompson Robert E RE Ripoll-Rozada Jorge J Wu Mike M Alwis Imala I Gori Alessandro A Loh Choy-Theng CT Parker Benjamin L BL Otting Gottfried G Jackson Shaun S Pereira Pedro José Barbosa PJB Payne Richard J RJ

ACS central science 20180328 4

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</ ...[more]

PMID: 29721529

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Mosquito-Derived Anophelin Sulfoproteins Are Potent Antithrombotics.

Publications

Mosquito-Derived Anophelin Sulfoproteins Are Potent Antithrombotics.

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