Identification of potential targets for an anticoagulant pectin.
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.



The 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.
Instituto Carlos Chagas, FIOCRUZ/PR, Brazil; Universidade Federal do Paraná (UFPR), Departamento de Bioquímica e Biologia Molecular, Brazil.
Aline Guimarães
AG
Santana
Universidade Federal do Paraná (UFPR), Departamento de Bioquímica e Biologia Molecular, Brazil.
Ana Helena Pereira
AH
Gracher
Universidade Federal do Paraná (UFPR), Departamento de Química, Brazil.
André Luis
AL
Rüdiger
Instituto Carlos Chagas, FIOCRUZ/PR, Brazil.
Nilson Ivo Tonin
NI
Zanchin
Instituto Carlos Chagas, FIOCRUZ/PR, Brazil.
Paulo Costa
PC
Carvalho
Universidade Federal do Paraná (UFPR), Departamento de Bioquímica e Biologia Molecular, Brazil.
Thales Ricardo
TR
Cipriani
Instituto Carlos Chagas, FIOCRUZ/PR, Brazil. Electronic address: tatianabrasil@fiocruz.br.
Tatiana
T
de Arruda Campos Brasil de Souza
D000925:Anticoagulants / Q000737:chemistry*; D000991:Antithrombins / Q000378:metabolism; D032084:Citrus sinensis / Q000737:chemistry*; D015844:Heparin Cofactor II / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D010368:Pectins / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D011485:Protein Binding; D040901:Proteomics; D013431:Sulfates / Q000737:chemistry; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism
D000925:Anticoagulants; D000991:Antithrombins; D013431:Sulfates; D015844:Heparin Cofactor II; D010368:Pectins; D013917:Thrombin
Anticoagulant; Molecular targets; Sulfated pectin