Year : 2014  |  Volume : 5  |  Issue : 1  |  Page : 36-42

Elucidating the specificity of non-heparin-based conformational activators of antithrombin for factor Xa inhibition

1 Department of Bio Sciences, Protein Conformation and Enzymology Lab, New Delhi, India
2 Department of Organic Synthesis Lab, Jamia Millia Islamia, New Delhi, India

Correspondence Address:
Mohamad Aman Jairajpuri
Department of Bio-Sciences, Protein Conformation and Enzymology Lab, Jamia Millia Islamia (A Central University), Jamia Nagar, New Delhi - 110 025
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0976-9668.127282

Rights and Permissions

Introduction: Antithrombin, the principal inhibitor of coagulation proteases, requires allosteric activation by its physiological cofactor, heparin or heparin sulfate to achieve physiologically permissible rates. This forms the basis of heparin's use as a clinical anticoagulant. However, heparin therapy is beset with severe complications, giving rise to the need to search new non-heparin activators of antithrombin, devoid of these complications and with favorable safety profiles. Materials and Methods: We chose some representative organic compounds that have been shown to be involved in coagulation modulation by affecting antithrombin and applied a blind docking protocol to find the binding energy and interactions of the modified (sulfated) versus unmodified organic scaffolds. Results and Conclusion: Increased sulfation plays a key role in shifting the specificity of organic compounds like quercetin, diosmin, rutin, mangiferin, isomangostin, Trapezifolixanthone and benzofuran towards the heparin binding site (HBS). However, in hesperetin and tetrahydroisoquinoline, sulfation shifts the specificity away from HBS. We have further tried to elucidate changes in the binding affinity of quercetin on account of gradual increase in the number of hydroxyl groups being substituted by sulfate groups. The results show gradual increase in binding energy with increase in sulfation. A theoretical screening approach is an ideal mechanism to predict lead molecules as activators of antithrombin and in determining the specificity for antithrombin.

Print this article     Email this article
 Next article
 Previous article
 Table of Contents

 Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
 Citation Manager
 Access Statistics
 Reader Comments
 Email Alert *
 Add to My List *
 * Requires registration (Free)

 Article Access Statistics
    PDF Downloaded399    
    Comments [Add]    
    Cited by others 3    

Recommend this journal