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Aprotinin binding to amyloid fibrils
I Cardoso1, P J Pereira, A M Damas
1Amyloid Unit, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
European Journal of Biochemistry
|April 12, 2000
Summary
Aprotinin binds to various amyloid fibrils, including insulin and transthyretin, through beta-sheet interactions. This proteinase inhibitor shows specific binding to amyloid deposits, not precursors, offering insights into amyloid detection and therapeutic strategies.
Area of Science:
- Biochemistry
- Molecular Biology
- Medical Imaging
Background:
- Amyloid deposits are characterized by beta-sheet structures.
- Thioflavin T and Congo Red are known amyloid markers, but their interaction details are unclear.
- Aprotinin is a radiopharmaceutical used for imaging immunoglobulin-type amyloidosis.
Purpose of the Study:
- To investigate aprotinin's binding to different types of amyloid fibrils.
- To elucidate the molecular nature and characteristics of aprotinin-amyloid interactions.
- To explore aprotinin's potential as a broader amyloid-targeting agent.
Main Methods:
- Dot-blot ligand-binding assays were used to test aprotinin binding.
- Scatchard analysis determined the binding affinity (Ka) to insulin amyloid fibrils.
- Competition experiments with analogues assessed binding specificity and mechanisms.
Main Results:
- Aprotinin specifically binds to insulin, transthyretin, beta-amyloid peptide, and immunoglobulin amyloid fibrils.
- Aprotinin does not bind to amorphous precipitates or soluble fibril precursors.
- Binding involves beta-sheet pairing, with a potential electrostatic component, and has a Ka of 2.9 microM-1 for insulin amyloid.
Conclusions:
- Aprotinin exhibits specific binding to a range of amyloid fibril types.
- The interaction mechanism involves beta-sheet pairing and potentially electrostatic forces.
- Aprotinin's binding characteristics suggest its utility beyond immunoglobulin-type amyloidosis.