AFM investigation of APAC (antiplatelet and anticoagulant heparin proteoglycan)
| Autor: | Riitta Lassila, Laurin Lux, Georg Ramer, Gernot Friedbacher, Bernhard Lendl, Annukka Jouppila, Maximilian Winzely, Karina Barreiro |
|---|---|
| Přispěvatelé: | Clinicum, Research Program in Systems Oncology, Institute for Molecular Medicine Finland, HUS Comprehensive Cancer Center, Hematologian yksikkö |
| Rok vydání: | 2021 |
| Předmět: |
VON-WILLEBRAND-FACTOR
medicine.drug_class Pharmacology Microscopy Atomic Force Heparin proteoglycan Biochemistry FORCE Analytical Chemistry Atomic force microscopy Von Willebrand factor In vivo Spectroscopy Fourier Transform Infrared BINDING Antithrombotic AFM-IR medicine Humans Antiplatelet Platelet Paper in Forefront SPECTROSCOPY biology Heparin Chemistry Anticoagulant Anticoagulants APAC DNA Photothermal-induced resonance Coagulation MICA biology.protein 1182 Biochemistry cell and molecular biology Proteoglycans 3111 Biomedicine AFM Platelet Aggregation Inhibitors |
| Zdroj: | Analytical and Bioanalytical Chemistry |
| ISSN: | 1618-2650 1618-2642 |
| DOI: | 10.1007/s00216-021-03765-y |
| Popis: | Antiplatelet and anticoagulant drugs are classified antithrombotic agents with the purpose to reduce blood clot formation. For a successful treatment of many known complex cardiovascular diseases driven by platelet and/or coagulation activity, the need of more than one antithrombotic agent is inevitable. However, combining drugs with different mechanisms of action enhances risk of bleeding. Dual anticoagulant and antiplatelet (APAC), a novel semisynthetic antithrombotic molecule, provides both anticoagulant and antiplatelet properties in preclinical studies. APAC is entering clinical studies with this new exciting approach to manage cardiovascular diseases. For a better understanding of the biological function of APAC, comprehensive knowledge of its structure is essential. In this study, atomic force microscopy (AFM) was used to characterize APAC according to its structure and to investigate the molecular interaction of APAC with von Willebrand factor (VWF), since specific binding of APAC to VWF could reduce platelet accumulation at vascular injury sites. By the optimization of drop-casting experiments, we were able to determine the volume of an individual APAC molecule at around 600 nm3, and confirm that APAC forms multimers, especially dimers and trimers under the experimental conditions. By studying the drop-casting behavior of APAC and VWF individually, we depictured their interaction by using an indirect approach. Moreover, in vitro and in vivo conducted experiments in pigs supported the AFM results further. Finally, the successful adsorption of APAC to a flat gold surface was confirmed by using photothermal-induced resonance, whereby attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) served as a reference method. Graphical abstract |
| Databáze: | OpenAIRE |
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