Identification of potential targets for an anticoagulant pectin

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• 作者：Aline Guimarã ; es Santana^a ; ^b ; Ana Helena Pereira Gracher^b ; André ; Luis Rü ; diger^c ; Nilson Ivo Tonin Zanchin^a ; Paulo Costa Carvalho^a ; Thales Ricardo Cipriani^b ; Tatiana de Arruda Campos Brasil de Souza^a ; ^{tatianabrasil@fiocruz.br}
• 关键词：Sulfated pectin ; Anticoagulant ; Molecular targets
• 刊名：Journal of Proteomics
• 出版年：2017
• 出版时间：16 January 2017
• 年：2017
• 卷：151
• 期：Complete
• 页码：243-250
• 全文大小：979 K
• 卷排序：151

文摘

Heparin is a sulfated polysaccharide of animal origin showing excellent anticoagulant properties. Although it strongly inhibits the coagulation cascade, its interaction with multiple sites results in several side effects. An ideal alternative compound should not only possess anticoagulant and antithrombotic activities, but also provide specific binding to components of the coagulation cascade to decrease side effects and facilitate the control of pharmacologic actions in patient's body. In this work, we performed a scan of potential targets for chemically sulfated pectin from Citrus sinensis (SCP) that shows an efficient anticoagulant activity by combining proteomics and molecular docking techniques. Defining the interaction partners of SCP is fundamental to evaluate if its pharmacological side effects can be as harmful as those from heparin. SCP interacts directly with heparin cofactor II, probably favoring its interaction with thrombin. SCP interaction with antithrombin depends likely on its association with thrombin or factor Xa. In addition to the interaction with factors related to homeostasis, SCP may also act on the renin-angiotensin and on the complement systems.Biological significanceThe knowledge of potential molecular targets of SCP provides clues to understand its mechanism of action in order to guide molecular changes in this compound to increase its specificity.