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
Related Articles
- EP ID EP14023
- DOI -
- Views 280
- Downloads 10
Embolization of Ruptured Hepatic Hydatid Cyst to Pulmonary Artery in an Elderly Patient Multidetector computed tomography fndings
Pulmonary embolism due to hydatid disease is an unusual condition resulting from the rupture of a hydatic heart cyst or the opening of liver hydatidosis into the venous circulation. A 78-year old male patient complaini...
Characteristics of Critically-Ill Patients at Two Tertiary Care Hospitals in Sudan.
Objectives: Knowledge of intensive care unit (ICU) admission patterns and characteristics is necessary for the development of critical care services, particularly in low-resource settings. This study aimed to describe th...
First International Nursing Conference Oman Innovations in Nursing Education and Practice Leading to Quality Care Sultan Qaboos University, Oman, 28–29th November 2011
Reconstruction of Exenterated Orbit using Combined Surgical and Prosthetic Approach
Reconstruction of an exenterated orbit remains a challenge. Orbital prostheses are nowadays are made of silicone elastomers. A major limitation with silicone orbital prostheses is their relatively short life span. Tis...
Porcelain Gallbladder Decoding the malignant truth
Gallbladder calcifcation, also referred to as porcelain gallbladder, has received signifcant attention in the medical literature due to its perceived role in increasing the risk of developing a gallbladder carcinoma. H...