Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis
書誌事項
- 公開日
- 2002-05
- 権利情報
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- http://www.springer.com/tdm
- DOI
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- 10.1038/417254a
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes.
収録刊行物
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- Nature
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Nature 417 (6886), 254-259, 2002-05
Springer Science and Business Media LLC
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キーワード
- Models, Molecular
- Protein Structure
- Pyrrolidines
- Carboxylic Acids
- Crystallography, X-Ray
- Quaternary
- Inhibitory Concentration 50
- Mice
- Models
- /dk/atira/pure/core/subjects/biomedicalsciences
- Animals
- Humans
- Protein Structure, Quaternary
- Crystallography
- Molecular
- Biomedical Sciences
- Amyloidosis
- Serum Amyloid P-Component
- Cross-Linking Reagents
- Liver
- X-Ray
- Calcium
- Dimerization
- Protein Binding
詳細情報 詳細情報について
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- CRID
- 1362825895162573440
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- NII論文ID
- 30013825861
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- DOI
- 10.1038/417254a
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- ISSN
- 14764687
- 00280836
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- PubMed
- 12015581
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- データソース種別
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- Crossref
- CiNii Articles
- OpenAIRE
