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

Wzorek, Joanna; Bednarek, Radosław; Watała, Cezary; Boncler, Magdalena

doi:10.1016/j.bcp.2020.113827

Cited by 6 publications

(13 citation statements)

References 49 publications

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“…Recently, we found that PSB 0777 significantly inhibits platelet aggregation and enhances the antiplatelet effects of cangrelor, but its antiplatelet activity strongly depends on the presence of plasma or HSA. Moreover, using SPR technology, the binding of PSB 0777 to HSA was detected with the affinity of 8.06 × 10 −5 M (Boncler et al, 2018;Wzorek et al, 2020). As regards cangrelor, it has been reported that it is strongly bound to plasma proteins (Keating, 2015), however, there is neither direct nor indirect evidence of cangrelor binding to albumin.…”

Section: Discussionmentioning

confidence: 99%

“…The binding of cangrelor to immobilized human serum albumin was assessed by surface plasmon resonance spectroscopy using the Biacore X system (Biacore AG, Uppsala, Sweden). The experiments were carried out on a dual channel CM5 sensor chip in PBS buffer, pH 7.4, containing 0.005% surfactant P20 as previously described (Wzorek et al, 2020). Briefly, 100 µg of HSA was dissolved in 1 ml of 10 mM sodium acetate buffer, pH 4.0, and immobilized on the flow cell 1 of the sensor chip surface.…”

Section: Surface Plasmon Resonance Measurementsmentioning

confidence: 99%

“…All individuals provided their written informed consent to participate in the study. The exclusion criteria were the same as described previously (Wzorek et al, 2020). The study was approved by the Human Studies Committee of the Medical University of Lodz (Poland) and was conducted in accordance with the guidelines established by the Declaration of Helsinki.…”

Section: Subjects and Blood Sample Collectionmentioning

confidence: 99%

“…Cell response (a fraction of activated platelets) was measured after preincubation of samples with 17 nM (IC 50 ) cangrelor (Boncler et al, 2018) dissolved in PBS buffer (3 min, 37°C) followed by a 5-min stimulation with 10 μM ADP. The activated platelets were stained with antibodies prior to fixation as described previously (Wzorek et al, 2020). A total of 10,000 events were acquired in each experiment using a FACSCanto II flow cytometer and surface expression of CD62P (P-selectin) in platelets was analysed using FACS/Diva v. 6.0 software (Becton-Dickinson, Franklin Lakes, NJ, United States).…”

Section: Analysis Of Platelet Activationmentioning

confidence: 99%

“…Recently, one of the adenosine receptor agonists, PSB 0777, was found to effectively inhibit platelet function and potentiate the antiplatelet effects of the P2Y 12 receptor inhibitor, cangrelor (Boncler et al, 2018). Furthermore, HSA was revealed to interact with PSB 0777 and significantly reduce its antiplatelet activity (Wzorek et al, 2020). It is very likely that cangrelor also binds to HSA, as far as it highly binds to plasma proteins (97-98%) (Keating, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of a Combined Antiplatelet Therapy Is Not Affected by a Simultaneous Binding of Cangrelor and PSB 0777 to Albumin

et al. 2021

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Concurrent administration of two drugs may complicate the management of acute coronary syndromes: competitive drug displacement diminishes drug binding and alters drug pharmacodynamics. We investigated the interaction of two antiplatelet compounds (PSB 0777 and cangrelor) with human serum albumin (HSA) to determine whether they compete with one another for the binding to albumin. Both examined compounds have been earlier claimed to bind to HSA (PSB 0777) or plasma proteins (cangrelor). Fluorescence spectroscopy, surface plasmon resonance spectroscopy and molecular modeling indicated that PSB 0777 and cangrelor interacted with HSA with moderate affinity (KD∼10−5 M). The binding of cangrelor to HSA involved primarily hydrophobic interactions, while the interaction of PSB 0777 with HSA was driven by hydrophobic and electrostatic forces. It was found that PSB 0777 and cangrelor do not share the same binding site on the protein. Our findings highlight the importance of albumin in the transport of PSB 0777 and cangrelor and suggest that the antiplatelet activity of the examined compounds used in combination is not affected by competition-induced changes in drug binding to HSA.

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Section: Discussionmentioning

confidence: 99%

Section: Surface Plasmon Resonance Measurementsmentioning

confidence: 99%

Section: Subjects and Blood Sample Collectionmentioning

confidence: 99%

Section: Analysis Of Platelet Activationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of a Combined Antiplatelet Therapy Is Not Affected by a Simultaneous Binding of Cangrelor and PSB 0777 to Albumin

et al. 2021

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A Commercial Nonbinding Surface Effectively Reduces Fibrinogen Adsorption but Does Not Prevent Platelet Adhesion to Fibrinogen

Boncler

2023

Macromolecular Bioscience

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A commercial nonbinding surface effectively prevents protein adsorption; however, the platelet phenotype on this surface has yet to be defined. This study evaluates platelet adhesion and adsorption of several plasma/extracellular matrix (ECM) proteins to the nonbinding surface compared to other commonly used nontreated and high-binding surfaces. Platelet adhesion to uncoated microplates and those coated with fibrinogen or collagen is quantified by colorimetric assay. The binding capacity of the examined surfaces for plasma/ECM proteins is evaluated by measuring the relative and absolute protein adsorption. Compared to other surfaces, the nonbinding surface effectively prevents platelet adsorption, i.e. by 61-93% (Enzyme-Linked Immunosorbent Assay, ELISA), and reduces platelet adhesion, i.e. by 92%, when not coated with any protein. The nonbinding surface also decreases platelet deposition on collagen (up to 31%), but not fibrinogen. The nonbinding surface seems to be more of a low-fouling than nonfouling material, as it is able to reduce fibrinogen adsorption but not prevent platelet adhesion to fibrinogen. This feature should be considered when using the nonbinding surface for in vitro platelet testing.

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Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation

Letson,

Morris,

Dobson

2023

Pharmacology Res & Perspec

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IntroductionThe binding of drugs to plasma proteins is an important consideration in drug development. We have reported that the dose of adenosine, lidocaine, and magnesium (ALM) fluid therapy for resuscitation from hemorrhagic shock is nearly 3‐times higher for pigs than rats. Since lidocaine strongly binds to serum alpha‐1‐acid glycoprotein (AGP), the aim of the study was to investigate the effect of hemorrhagic shock on levels of AGP in rats and pigs.Materials and MethodsHealthy adult male Sprague–Dawley rats and female crossbred pigs (n = 33 each) underwent tail vein and peripheral ear vein blood sampling, respectively, to collect plasma for AGP measurements. Rats (n = 17) and pigs (n = 16) underwent surgical instrumentation and uncontrolled hemorrhage via liver resection, and were treated with 3% NaCl ± ALM IV bolus followed 60 min later by 4 h 0.9% NaCl ± ALM IV drip. Rats were monitored for 72 h with blood samples taken post‐surgery, and at 5.25, 24, and 72 h. Pigs were monitored for 6 h with blood samples taken post‐surgery, and at 60 min and 6 h. Plasma AGP was measured with rat‐ and pig‐specific enzyme‐linked immunosorbent assay kits.ResultsBaseline AGP levels in rats were 3.91 μg/mL and significantly 83‐fold lower than in pigs (325 μg/mL). Surgical instrumentation was associated with ~10‐fold increases in AGP in rats and a 21% fall in pigs. AGP levels remained elevated in rats after hemorrhage and resuscitation (28–29 μg/mL). In contrast, no significant differences in plasma AGP were found in ALM‐ or Saline‐treated pigs over the monitoring period.ConclusionsWe conclude that the trauma of surgery alone was associated with significant increases in AGP in rats, compared to a contrasting decrease in pigs. Higher levels of plasma AGP in pigs prior to hemorrhagic shock is consistent with the higher ALM doses required to resuscitate pigs compared with rats.

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

Cited by 6 publications

References 49 publications

Efficacy of a Combined Antiplatelet Therapy Is Not Affected by a Simultaneous Binding of Cangrelor and PSB 0777 to Albumin

Efficacy of a Combined Antiplatelet Therapy Is Not Affected by a Simultaneous Binding of Cangrelor and PSB 0777 to Albumin

A Commercial Nonbinding Surface Effectively Reduces Fibrinogen Adsorption but Does Not Prevent Platelet Adhesion to Fibrinogen

Changes in plasma alpha‐1 acid glycoprotein following hemorrhagic trauma: Possible role in dose differences of ALM drug therapy in rat and pig resuscitation

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