Binding of adenosine derivatives to carrier proteins may reduce their antiplatelet activity.

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Wzorek J, Bednarek R, Watala C, Boncler M

Binding of adenosine derivatives to carrier proteins may reduce their antiplatelet activity.

Biochem Pharmacol. 2020 Apr;174:113827. doi: 10.1016/j.bcp.2020.113827. Epub 2020 Jan 25.

PubMed ID

31987853 [ View in PubMed

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Abstract

Adenosine analogues have high affinity and selectivity for adenosine receptors (AR), and exhibit anti-platelet activity. Plasma proteins play an important role in the regulation of platelet function and may influence the action of anti-platelet compounds. Little is known about the interactions of AR agonists with plasma proteins. This study investigates the interplay between AR agonists and plasma proteins and the consequences of those interactions. Surface plasmon resonance was employed together with molecular docking study to determine the binding kinetics of four selected ARagonists (PSB0777, Cl-Ado, MRE0094, UK432097) to several carrier proteins and to clarify the nature of these interactions. The influence of a whole plasma and of some plasma components on the effectiveness of ARagonists in the inhibition of platelet function was assessed by flow cytometry (platelet activation) and ELISA (platelet adhesion). Plasma proteins remarkably diminished the effectiveness of ARagonists in inhibiting platelet activation and adhesion in vitro. ARagonists were found to strongly bind to human serum albumin (HSA) and the protein components of lipoproteins - apolipoproteins; HSA was essential for the binding of water-soluble PSB0777, whereas apolipoproteins were needed for interactions with poorly-water soluble compounds such as UK432097 and MRE0094. In addition, HSA was shown to significantly reduce the effectiveness of PSB0777 in inhibiting ADP-induced platelet activation. In conclusion, HSA and lipoproteins are important carriers for ARagonists, which can affect pharmacodynamics of ARagonists used as platelet inhibitors.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Adenosine	Serum albumin	Protein	Humans	Unknown	Binder	Details