In Silico Design of Novel Anticoagulant Peptides targeting Blood Coagulation Factor VIIa
Journal Title: Sultan Qaboos University Medical Journal - Year 2011, Vol 11, Issue 1
Abstract
Objectives: Te coagulation cascade initiated during vascular injury prevents bleeding. Unwanted clot formation is however detrimental and requires the use of anticoagulants for prophylaxis and treatment. Anticoagulants targeting a specifc step or an enzyme in the clotting process are most preferred as they minimise disadvantageous side-effects. A principal step in the discovery of novel anticoagulants encompasses the in silico design of potential leads. Tis study depicts the in silico design of peptide anticoagulants targeting coagulation factor VIIa. Methods: Applying the proline bracket rule and using various bioinformatics tools: the basic alignment search tool (BLAST) of National Center for Biotechnology Information; the T-coffee module provided by European Molecular Biology Laboratory-European Bioinformatics Institute, and several modules available on the ExPASy server, we designed fve bivalent chimeric anticoagulants targeting factor VIIa, using factor VIIa inhibitors – hemextin A from Hemachatus haemachatus (African Ringhals cobra) venom and factor VIIa exosite-inhibitor peptide as templates. Six peptides were derived from hemextin A, which were concomitantly fused with factor VIIa exosite-inhibitor peptide intermediated by a polyalanine spacer, and analysed for structural stability using the SWISS-MODEL software developed at the Swiss Institute of Bioinformatics and WebLab ViewerPro (Version 4.2). Results: Twelve chimeric peptides were obtained; only fve exhibited stable structures in silico. Conclusion: Te fve peptides obtained are probable anticoagulant leads that should be further evaluated using suitable in vitro and in vivo assays. Further, this study shows how simple web-based modules can be used for the rational design of probable leads targeting specifc physiological molecular targets.
Authors and Affiliations
Manal S Q Al-Amri| Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman, Khalid Alrasadi| Department of Biochemistry, Sultan Qaboos University Hospital, Muscat, Oman, Riad Bayoumi| Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman, Yajnavalka Banerjee| Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
Keywords
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In Silico Design of Novel Anticoagulant Peptides targeting Blood Coagulation Factor VIIa
Objectives: Te coagulation cascade initiated during vascular injury prevents bleeding. Unwanted clot formation is however detrimental and requires the use of anticoagulants for prophylaxis and treatment. Anticoagulants...