In Silico design of novel anticoagulant peptides targeting blood coagulation factor VIIa

Manal S Q Al-Amri, Khalid Alrasadi, Riad Bayoumi, Yajnavalka Banerjee

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)83-94
Number of pages12
JournalSultan Qaboos University Medical Journal
Volume11
Issue number1
Publication statusPublished - Feb 2011

Fingerprint

Factor VIIa
Blood Coagulation Factors
Computer Simulation
Anticoagulants
Elapidae
Peptides
Computational Biology
Information Centers
Vascular System Injuries
Coffee
Biotechnology
Proline
Molecular Biology
Software
Hemorrhage

Keywords

  • Anticoagulant
  • Factor VIIa
  • In silico drug design

ASJC Scopus subject areas

  • Medicine(all)

Cite this

In Silico design of novel anticoagulant peptides targeting blood coagulation factor VIIa. / Al-Amri, Manal S Q; Alrasadi, Khalid; Bayoumi, Riad; Banerjee, Yajnavalka.

In: Sultan Qaboos University Medical Journal, Vol. 11, No. 1, 02.2011, p. 83-94.

Research output: Contribution to journalArticle

Al-Amri, Manal S Q ; Alrasadi, Khalid ; Bayoumi, Riad ; Banerjee, Yajnavalka. / In Silico design of novel anticoagulant peptides targeting blood coagulation factor VIIa. In: Sultan Qaboos University Medical Journal. 2011 ; Vol. 11, No. 1. pp. 83-94.
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