Mosquito-Derived Anophelin Sulfoproteins Are Potent Antithrombotics
| العنوان: | Mosquito-Derived Anophelin Sulfoproteins Are Potent Antithrombotics |
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| المؤلفون: | Imala Alwis, Jorge Ripoll-Rozada, Pedro Pereira, Choy-Theng Loh, Mike Wu, Robert E. Thompson, Gottfried Otting, Shaun P. Jackson, Emma E. Watson, Xuyu Liu, Richard J. Payne, Benjamin L. Parker, Alessandro Gori |
| المساهمون: | Instituto de Investigação e Inovação em Saúde |
| المصدر: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP ACS Central Science, Vol 4, Iss 4, Pp 468-476 (2018) ACS Central Science |
| بيانات النشر: | American Chemical Society (ACS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Tyrosine sulfation, biology, Chemistry, General Chemical Engineering, Anopheles gambiae, Anopheles, General Chemistry, biology.organism_classification, 3. Good health, 03 medical and health sciences, 030104 developmental biology, Thrombin, Sulfation, Biochemistry, Anopheles albimanus, In vivo, 030406 - Proteins and Peptides [FoR], medicine, Tyrosine, 030405 - Molecular Medicine [FoR], QD1-999, Research Article, medicine.drug |
| الوصف: | 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. Anophelin proteins from the saliva of the Anopheles mosquito possess potent thrombin inhibitory and anticoagulant activity when post-translationally sulfated on conserved tyrosine residues. |
| وصف الملف: | application/pdf |
| تدمد: | 2374-7951 2374-7943 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df3458cdb95b6867cf76f215a2669021 https://doi.org/10.1021/acscentsci.7b00612 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....df3458cdb95b6867cf76f215a2669021 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 23747951 23747943 |
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