JP4235544B2 - 欠陥折畳み蛋白質センサー方法 - Google Patents
欠陥折畳み蛋白質センサー方法 Download PDFInfo
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- JP4235544B2 JP4235544B2 JP2003500572A JP2003500572A JP4235544B2 JP 4235544 B2 JP4235544 B2 JP 4235544B2 JP 2003500572 A JP2003500572 A JP 2003500572A JP 2003500572 A JP2003500572 A JP 2003500572A JP 4235544 B2 JP4235544 B2 JP 4235544B2
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
- G01N33/542—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
- G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2814—Dementia; Cognitive disorders
- G01N2800/2828—Prion diseases
Description
Bucciantini、M.他(2002)「Inherent Toxicity of Aggregates Implies a Common Mechanism for Protein Misfolding Diseases。Nature 416:507−511。
1 Clayton Thomas、「Tabor’s Cyclopedic Medical Dictionary」(Phil.、F. A. Davis Company、1989)、1485。
2 Ivan Roitt他、「Immunology」(Mosby−Year Book Europe Limited、1993)、15.1。
3 Benjamin Lewin、「Genes IV」(Oxford Univ. Press、New York、1990)、108。
4 Fred E. Cohen他、「Pathologic Conformations of Prion Proteins(Annu. Rev. Biochem. 1998)」67:793−819。
12:βシート二量体
14:ペプチドプローブ
15:分枝状生物学的構造体
16:βシート構造体
18:集合
20:テスト試料
Claims (22)
- 優勢的なβシート二次構造を含む、欠陥折畳み蛋白質粒子を検知する方法であって
(a) 体液を含むテスト試料に、ペプチドプローブを添加することにより混合物を形成する工程であって、
(i) 該ペプチドプローブが、
(1) 該蛋白質粒子の蛋白質の断片、
(2) ポリリシン配列、及び
(3) ポリグルタミン配列
からなる群より選択されるアミノ酸配列を含むペプチドであり、もし、該蛋白質粒子がプリオン蛋白質を含む場合には、該アミノ酸配列は、プリオン蛋白質の前向き方向の断片に対応する第一のアミノ酸配列、及び、プリオン蛋白質の逆向き方向の断片に対応する第二のアミノ酸配列を含み、
(ii) 該ペプチドが、該蛋白質粒子と相互作用する優勢α - 螺旋及び / 若しくはランダムコイルの二次構造を有し、及び、
(iii) 該ペプチドが、欠陥折畳み蛋白質粒子との接触、または、このような構造的移行をしたその他のこのようなペプチドプローブとの接触により、α - 螺旋及び / 若しくはランダムコイルの二次構造の減少、並びに、βシート二次構造の増加に向けて構造的に移行する
工程;
(b) ペプチドプローブとテスト試料中のあらゆる欠陥折畳み蛋白質粒子とを相互反応させる工程;並びに
(c)混合物中におけるβシート二次構造の増加を検知する工程であって、該増加の少なくとも一部分は、該ペプチドプローブのβシート二次構造の増加によるものであり、いずれのこのような増加が、該テスト試料中の欠陥折畳み蛋白質粒子の存在を示す工程
を含む方法。 - 該ペプチドプローブが光学検知可能ラベル付きペプチドである、請求項1に記載の方法。
- 該体液が、動物中では実質的に液体形体で存在する液体を含む、請求項 1 または 2 に記載の方法。
- 該体液が、希釈液を動物中で実質的に液体形態で存在する液体と一緒に含む、請求項 1 から 3 のいずれか一項に記載の方法。
- 該ペプチドプローブが感染性でなく、そして、試料に該ペプチドプローブを添加する工程が、該工程の実行者に対して感染の面から有害でない、請求項 1 から 4 のいずれか一項に記載の方法。
- 該ペプチドプローブが感染性でなく、そして混合物中のβシート二次構造の増加を検知する工程が、該工程の実行者に対して感染の面から有害でない、請求項1から 5 のいずれか一項に記載の方法。
- 該検知の工程が、光学的測定または構造的測定を行うことを含む、請求項 1 から 6 のいずれか一項に記載の方法。
- 該検知工程が、光散乱及び円偏光二色性、またはそれらの組合せから選択される分析技術を用いて構造的検知を行うことを含む、請求項 7 に記載の方法。
- 該方法がさらに、試料にペプチドプローブを添加する工程の前に、試料を分解技術に付すことを含む、請求項 1 から 8 のいずれか一項に記載の方法。
- 該体液が生きた動物より取得されたものである、請求項1から 9 のいずれか一項に記載の方法。
- 該体液が血液、脳脊髄液、またはリンパ液を含む、請求項 1 から10のいずれか一項に記載の方法。
- 該ペプチドプローブが感染性でない、請求項 1 から 11 のいずれか一項に記載の方法。
- 該蛋白質粒子が伝達性スポンジ形態脳病( TSE )と関連付けられる PrP SC を含む、請求項 1 に記載の方法。
- 該ペプチドプローブがポリリシンアミノ酸配列を含む、請求項 1 から 13 のいずれか一項に記載の方法。
- 該蛋白質粒子が該クロイツフェルト - ヤコブ症と関連付けられる PrP SC を含む、請求項 1 に記載の方法。
- 該蛋白質粒子がスクラピーと関連付けられる PrP SC を含む、請求項 1 に記載の方法。
- 該ペプチドプローブが蛍光標識を含み、そして、該検知工程が該ペプチドプローブの蛍光を検知することを含む、請求項 2 に記載の方法。
- 該蛋白質粒子が疾病関連蛋白質である、請求項 1 から 17 のいずれか一項に記載の方法。
- 該ペプチドが螺旋 - ループ構造を有する、請求項 1 から 18 のいずれか一項に記載の方法。
- 該蛋白質粒子がプリオン蛋白質を含み、そして該ペプチドが、プリオン蛋白質の非病原性形体と比べて、プリオン蛋白質の病原性形体と優先的に相互作用する、請求項 1 に記載の方法。
- 該ペプチドが配列番号 10 を含む、請求項 20 に記載の方法。
- 該蛋白質が、βアミロイド蛋白質、ハンチントン蛋白質、または腫瘍関連細胞表面 NADH オキシダーゼ (+NOX) からなる群より選択される、請求項18に記載の方法。
Applications Claiming Priority (2)
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US29545601P | 2001-05-31 | 2001-05-31 | |
PCT/US2002/017212 WO2002097444A2 (en) | 2001-05-31 | 2002-05-30 | Misfolded protein sensor method |
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JP2004536296A JP2004536296A (ja) | 2004-12-02 |
JP4235544B2 true JP4235544B2 (ja) | 2009-03-11 |
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JP2003500572A Expired - Fee Related JP4235544B2 (ja) | 2001-05-31 | 2002-05-30 | 欠陥折畳み蛋白質センサー方法 |
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US (4) | US7691639B2 (ja) |
EP (1) | EP1395833B1 (ja) |
JP (1) | JP4235544B2 (ja) |
AU (2) | AU2002320045B2 (ja) |
CA (1) | CA2448981C (ja) |
MX (1) | MXPA03011000A (ja) |
WO (1) | WO2002097444A2 (ja) |
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JP3910569B2 (ja) * | 2003-08-19 | 2007-04-25 | 独立行政法人科学技術振興機構 | アミロイドβ蛋白質のアミロイド線維化を増幅するための試薬 |
US20060057671A1 (en) * | 2004-09-10 | 2006-03-16 | Orser Cindy S | Immobilized probes and methods of detecting conformationally altered prion proteins |
CN101156068B (zh) | 2005-02-15 | 2015-03-18 | 阿德利夫股份有限公司 | 检测错折叠蛋白和朊病毒的方法 |
JP5097206B2 (ja) * | 2006-07-28 | 2012-12-12 | エイディーライフ インコーポレイティッド | 診断および治療のためのペプチドプローブ |
JP2011517666A (ja) | 2008-03-21 | 2011-06-16 | エイディーライフ インコーポレイティッド | 血液脳関門を横断してペプチドを運搬するためのピレンの使用 |
WO2009117042A1 (en) | 2008-03-21 | 2009-09-24 | Adlyfe, Inc. | Use of pyrene to carry non-peptide agents across the blood brain barrier |
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AU2008203542A1 (en) | 2008-08-28 |
EP1395833A2 (en) | 2004-03-10 |
US8062895B2 (en) | 2011-11-22 |
US7166471B2 (en) | 2007-01-23 |
WO2002097444A2 (en) | 2002-12-05 |
US20100267151A1 (en) | 2010-10-21 |
JP2004536296A (ja) | 2004-12-02 |
AU2002320045B2 (en) | 2008-05-08 |
EP1395833B1 (en) | 2013-02-27 |
WO2002097444A3 (en) | 2003-10-30 |
US7691639B2 (en) | 2010-04-06 |
MXPA03011000A (es) | 2004-02-27 |
CA2448981C (en) | 2014-03-18 |
US20060275910A1 (en) | 2006-12-07 |
AU2008203542B2 (en) | 2011-01-20 |
US20030104633A1 (en) | 2003-06-05 |
US20060286672A1 (en) | 2006-12-21 |
CA2448981A1 (en) | 2002-12-05 |
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