Target Specific Anticoagulant Peptides: A Review
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Anticoagulant drugs are of crucial importance for the treatment and prophylaxis of thrombotic disorders. The use of traditional anticoagulants like heparin and warfarin is majorly associated with bleeding complications. In the quest for safer anticoagulation therapy, the interest for the isolation of novel anticoagulant compounds has shifted towards natural sources. Peptides can be considered as better alternative due to their therapeutic potential in the treatment of diseases. Peptides from hematophagous (blood-feeding) and venomous organisms have been recognized as potential anticoagulant agents. Of late, peptides derived from the hydrolysis of food proteins, including edible seaweeds, milk and seed proteins, have also shown to possess promising in vitro anticoagulant activity. To overcome the problems associated with regular anticoagulants, peptides targeting vital steps in the clotting cascade have been studied. This review focuses on anticoagulant peptides with known targets, inhibiting crucial factors in the coagulation cascade such as FXa, FXIa, FXIIa and FVIIa/TF complex, as well as peptides with unknown targets.
KeywordsAnticoagulants Peptides Thrombosis Coagulation
The authors are grateful to the management of Vellore Institute of Technology for their encouragement and providing financial support to write this review article.
Compliance with Ethical Standards
Conflict of interest
Azeemullah A. Syed and Alka Mehta declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- Bergum PW, Cruikshank A, Maki SL et al (2001) Role of zymogen and activated factor X as scaffolds for the inhibition of the blood coagulation factor VIIa-tissue factor complex by recombinant nematode anticoagulant protein c2. J Biol Chem 276:10063–10071. https://doi.org/10.1074/jbc.M009116200 CrossRefPubMedGoogle Scholar
- Deng L, He Q, Kang T et al (2010) Biochemical and biophysical research communications identification of an anticoagulant peptide that inhibits both fXIa and fVIIa/tissue factor from the blood-feeding nematode Ancylostoma caninum. Biochem Biophys Res Commun 392:155–159. https://doi.org/10.1016/j.bbrc.2009.12.177 CrossRefGoogle Scholar
- Lee AY, Agnelli G, Büller H et al (2001) Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement. Circulation 104:74–78. https://doi.org/10.1161/hc2601.091386 CrossRefPubMedGoogle Scholar
- Mieszczanek J, Harrison LM, Vlasuk GP, Cappello M (2004a) Anticoagulant peptides from Ancylostoma caninum are immunologically distinct and localize to separate structures within the adult hookworm. Mol Biochem Parasitol 133:319–323. https://doi.org/10.1016/j.molbiopara.2003.10.015 CrossRefPubMedGoogle Scholar
- Mieszczanek J, Harrison LM, Cappello M (2004b) Ancylostoma ceylanicum anticoagulant peptide-1: role of the predicted reactive site amino acid in mediating inhibition of coagulation factors Xa and VIIa. Mol Biochem Parasitol 137:151–159. https://doi.org/10.1016/j.molbiopara.2004.05.011 CrossRefPubMedGoogle Scholar
- Moons AHM, Peters RJG, Bijsterveld NR, Piek JJ, Prins MH, Vlasuk GP, Rote WE, Buller HR (2003) Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty. J Am Coll Cardiol 41:2147–2153. https://doi.org/10.1016/S0735-1097(03)00478-9 CrossRefPubMedGoogle Scholar
- Murakami MT, Weaver SE, Tulinsky A et al (2007) Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagous nematode Ancylostoma caninum. J Mol Biol 366:602–610. https://doi.org/10.1016/j.jmb.2006.11.040 CrossRefPubMedGoogle Scholar
- Ren Y, Yang Y, Wu W et al (2016) Identification and characterization of novel anticoagulant peptide with thrombolytic effect and nutrient oligopeptides with high branched chain amino acid from Whitmania pigra protein. Amino Acids 48:2657–2670. https://doi.org/10.1007/s00726-016-2299-8 CrossRefPubMedGoogle Scholar
- Rios-steiner JL, Murakami MT, Tulinsky A, Arni RK (2007) Active and exo-site inhibition of human factor Xa: structure of des-Gla factor Xa inhibited by NAP5, a potent nematode anticoagulant protein from Ancylostoma caninum. J Mol Biol 371:774–786. https://doi.org/10.1016/j.jmb.2007.05.042 CrossRefPubMedGoogle Scholar
- Rojas-Ronquillo R, Cruz-Guerrero A, Flores-Nájera A et al (2012) Antithrombotic and angiotensin-converting enzyme inhibitory properties of peptides released from bovine casein by Lactobacillus casei Shirota. Int Dairy J 26:147–154. https://doi.org/10.1016/j.idairyj.2012.05.002 CrossRefGoogle Scholar
- Secemsky EA, Kirtane A, Bangalore S et al (2016) Use and effectiveness of bivalirudin versus unfractionated heparin for percutaneous coronary intervention among patients with ST-segment elevation myocardial infarction in the United States. JACC 9:2376–2386. https://doi.org/10.1016/j.jcin.2016.09.020 PubMedGoogle Scholar
- Shin SC, Ahn IH, Ahn DH et al (2017) Characterization of two antimicrobial peptides from antarctic fishes (Notothenia coriiceps and Parachaenichthys charcoti). PLoS ONE 1–12. https://doi.org/10.1371/journal.pone.0170821
- Thakur R, Kumar A, Bose B et al (2014) A new peptide (Ruviprase) purified from the venom of Daboia russelii russelii shows potent anticoagulant activity via non-enzymatic inhibition of thrombin and factor Xa. Biochimie 105:149–158. https://doi.org/10.1016/j.biochi.2014.07.006 CrossRefPubMedGoogle Scholar