Next Article in Journal
A Conserved uORF Regulates APOBEC3G Translation and Is Targeted by HIV-1 Vif Protein to Repress the Antiviral Factor
Previous Article in Journal
Sensitive Electrochemical Detection of Phosphorylated-Tau Threonine 231 in Human Serum Using Interdigitated Wave-Shaped Electrode
 
 
Article

Screening of the Promising Direct Thrombin Inhibitors from Haematophagous Organisms. Part I: Recombinant Analogues and Their Antithrombotic Activity In Vitro

1
Laboratory of Biopharmaceutical Technologies, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Street, 16/10, 117997 Moscow, Russia
2
Biological Testing Laboratory, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia
3
Laboratory of Toxicology In Vitro, Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Pushchino, Prospekt Nauki, 6, 142290 Moscow, Russia
4
Altai Branch of FSBI, National Research Center for Hematology, Ministry of Healthcare of the Russian Federation, 656045 Barnaul, Russia
*
Authors to whom correspondence should be addressed.
Academic Editor: Matteo Di Minno
Biomedicines 2022, 10(1), 11; https://doi.org/10.3390/biomedicines10010011
Received: 15 November 2021 / Revised: 11 December 2021 / Accepted: 17 December 2021 / Published: 22 December 2021
(This article belongs to the Topic Compounds with Medicinal Value)
The success in treatment of venous thromboembolism and acute coronary syndromes using direct thrombin inhibitors has stimulated research aimed at finding a new anticoagulant from haematophagous organisms. This study deals with the comparison between hirudin-1 from Hirudomedicinalis(desirudin), being the first-known and most well-studied natural anticoagulant, along with recombinant analogs of haemadin from the leech Haemadipsa sylvestris, variegin from the tick Amblyomma variegatum, and anophelin from Anopheles albimanus. These polypeptides were chosen due to their high specificity and affinity for thrombin, as well as their distinctive inhibitory mechanisms. We have developed a universal scheme for the biotechnological production of these recombinant peptides as pharmaceutical substances. The anticoagulant activities of these peptides were compared using the thrombin amidolytic activity assay and prolongation of coagulation time (thrombin time, prothrombin time, and activated partial thromboplastin time) in mouse and human plasma. The preliminary results obtained suggest haemadin as the closest analog of recombinant hirudin-1, the active substance of the medicinal product Iprivask (Aventis Pharmaceuticals, USA) for the prevention of deep venous thrombosis in patients undergoing elective hip or knee replacement surgery. In contrast, variegin can be regarded as a natural analog of bivalirudin (Angiomax, The Medicines Company), a synthetic hirudin-1 derivative certified for the treatment of patients undergoing percutaneous coronary intervention and of patients with unstable angina pectoris after percutaneous transluminal coronary angioplasty. View Full-Text
Keywords: anticoagulant; direct thrombin inhibitor (DTI); haemadin; variegin; hirudin-1; anophelin; heparin; intein; coagulation time test anticoagulant; direct thrombin inhibitor (DTI); haemadin; variegin; hirudin-1; anophelin; heparin; intein; coagulation time test
Show Figures

Figure 1

MDPI and ACS Style

Kostromina, M.A.; Tukhovskaya, E.A.; Shaykhutdinova, E.R.; Slashcheva, G.A.; Ismailova, A.M.; Palikov, V.A.; Palikova, Y.A.; Dyachenko, I.A.; Kravchenko, I.N.; Sadovnikova, E.S.; Novikova, N.I.; Perepechenova, N.A.; Zayats, E.A.; Abramchik, Y.A.; Lykoshin, D.D.; Mamaev, A.N.; Grigorieva, E.V.; Momot, A.P.; Murashev, A.N.; Esipov, R.S. Screening of the Promising Direct Thrombin Inhibitors from Haematophagous Organisms. Part I: Recombinant Analogues and Their Antithrombotic Activity In Vitro. Biomedicines 2022, 10, 11. https://doi.org/10.3390/biomedicines10010011

AMA Style

Kostromina MA, Tukhovskaya EA, Shaykhutdinova ER, Slashcheva GA, Ismailova AM, Palikov VA, Palikova YA, Dyachenko IA, Kravchenko IN, Sadovnikova ES, Novikova NI, Perepechenova NA, Zayats EA, Abramchik YA, Lykoshin DD, Mamaev AN, Grigorieva EV, Momot AP, Murashev AN, Esipov RS. Screening of the Promising Direct Thrombin Inhibitors from Haematophagous Organisms. Part I: Recombinant Analogues and Their Antithrombotic Activity In Vitro. Biomedicines. 2022; 10(1):11. https://doi.org/10.3390/biomedicines10010011

Chicago/Turabian Style

Kostromina, Maria A., Elena A. Tukhovskaya, Elvira R. Shaykhutdinova, Gulsara A. Slashcheva, Alina M. Ismailova, Victor A. Palikov, Yuliya A. Palikova, Igor A. Dyachenko, Irina N. Kravchenko, Elena S. Sadovnikova, Nadezhda I. Novikova, Natalia A. Perepechenova, Evgeniy A. Zayats, Yuliya A. Abramchik, Dmitry D. Lykoshin, Andrey N. Mamaev, Elena V. Grigorieva, Andrey P. Momot, Arkady N. Murashev, and Roman S. Esipov. 2022. "Screening of the Promising Direct Thrombin Inhibitors from Haematophagous Organisms. Part I: Recombinant Analogues and Their Antithrombotic Activity In Vitro" Biomedicines 10, no. 1: 11. https://doi.org/10.3390/biomedicines10010011

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop