Aprotinin Protein
Description
Biochemical Characteristics
Aprotinin is a monomeric globular polypeptide composed of 58 amino acids arranged in a single chain stabilized by three disulfide bonds (Cys5-Cys55, Cys14-Cys38, Cys30-Cys51). Key properties include:
| Property | Value | Source |
|---|---|---|
| Molecular Weight | 6512 Da | |
| Isoelectric Point (pI) | 10.5 | |
| Amino Acid Sequence | RPDFCLEPPYTGPCKARIIRYFYNAK... | |
| Stability | Stable at pH 3–10, degrades at extremes |
Its basic nature arises from 10 positively charged residues (lysine/arginine) and only four acidic residues (aspartate/glutamate) .
Mechanism of Action
Aprotinin competitively inhibits serine proteases through reversible binding to their active sites :
Primary Targets and Inhibition Constants:
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Trypsin: IC₅₀ ≈ 0.1–0.2 µM
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Plasmin: IC₅₀ ≈ 0.3–0.5 µM
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Kallikrein: IC₅₀ ≈ 0.6–1.0 µM
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Chymotrypsin: IC₅₀ ≈ 2–5 µM
By inhibiting kallikrein, it suppresses the intrinsic coagulation pathway and fibrinolysis, reducing perioperative bleeding . Platelet glycoprotein stabilization (e.g., GpIb, GpIIb/IIIa) further enhances hemostatic effects .
Surgical Applications
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Cardiac Surgery: Meta-analyses show a 39% reduction in transfusion requirements during coronary artery bypass grafting (CABG) .
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Orthopedic Surgery: Reduced blood loss by 30–45% in high-risk procedures .
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Liver Transplantation: Early benefits were offset by toxicity concerns .
Antiviral Activity Against SARS-CoV-2
Recent trials highlight aprotinin’s repurposing potential:
Inhaled aprotinin shortened hospitalization by 5 days and reduced oxygen dependency in moderate COVID-19 patients .
Anti-Inflammatory Effects
While early studies suggested cytokine modulation (e.g., IL-6, TNF-α), a meta-analysis of 13 RCTs found no significant suppression of pro-inflammatory markers except IL-10 at low doses .
Research Use
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Laboratory: Prevents proteolysis during cell lysis (1–2 µg/mL) .
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Diagnostics: Stabilizes labile proteins (e.g., glucagon) in blood samples .
Ongoing Research Directions
Product Specs
The specific activity of the Aprotinin is measured as 6,120 KIU (Kallikrein Inactivator Units) per mg, determined at 3.4 pH according to European Pharmacopoeia Units (Eur.U/mg).
Product Science Overview
Aprotinin was primarily used to reduce perioperative blood loss and the need for blood transfusions in patients undergoing complex surgeries, such as heart and liver surgeries . By slowing down fibrinolysis, the process that leads to the breakdown of blood clots, aprotinin helps to minimize blood loss during surgery .
Aprotinin was marketed under the trade name Trasylol by Bayer and later by Nordic Group Pharmaceuticals . However, its use was temporarily suspended worldwide in 2007 after studies suggested an increased risk of complications or death associated with its use . In 2012, the European Medicines Agency (EMA) recommended lifting the suspension, allowing aprotinin to be used under restricted conditions .
