الملخص الإنجليزي
Objectives: The 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 specific 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. This 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 five 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 five exhibited stable structures in silico. Conclusion: The five 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 specific physiological molecular targets.
