JP2007000151A - エネルギー転移連結の色素によりラベルされたプローブ - Google Patents
エネルギー転移連結の色素によりラベルされたプローブ Download PDFInfo
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Abstract
【解決手段】ジデオキシターミネーション法において、ジデオキシヌクレオシドを用い、当該ジデオキシヌクレオシドは、ドナー蛍光団−受容体蛍光団対を含み、そして前記ドナー蛍光団から前記受容体蛍光団への効果的なエネルギーの転移を生じさせるものであり、前記個々のジデオキシヌクレオシドが実質的に同じ波長で吸光し、そして異なった波長で発光し;そして前記個々のジデオキシヌクレオシドが、当該ジデオキシヌクレオシド上の前記ドナー蛍光団−受容体蛍光団対のドナー蛍光団及びドナー蛍光団と受容体蛍光団との間の距離を変えることにより又は蛍光団自体を変えることにより前記分離において実質的に同じ移動性を有する、ことを特徴とする。
【選択図】なし
Description
特有の赤色シフトされた発光スペクトルを有する色素を選択できるので、それらの吸光最大値もまた、赤色に移動し、そしてすべての色素は同じレーザー源によりもはや効果的に励起され得ない。
従って、多くの構成成分が同じシステム及び一回の実施で決定され得るように、サンプルの多重化を可能にする改良された方法を提供することが実質的な興味の対象である。また、個々のラベルが、共通する波長で強い吸光性を有し、螢光のために高い収量を有し、発光の大きなストークスシフトを有し、種々の発光が個別であり、そしてラベルが同じ移動性シフトを導びくことが望まれる。単一色素により分子を単純にラベルすることによってそれらの矛盾する目的を達成することは困難である。
異なる複数のプライマーが PCRに使用される場合、個々のプライマーが本発明に従ってラベルされ、その結果、異なるプライマーの個々に対して相補的な標的配列の存在を容易に検出することができる。使用される他の用途は、特定の抗体を用いてのアイソザイムの同定、異なった多糖類を用いてのレクチンの同定、及び同様の同定を包含する。
キットは、マッチする約6種までの、通常約4種までの異なったラベルを有するが、しかし2〜6種の異なったラベルを有する、複数組のマッチするラベルを有することができる。
実験
遺伝子分析のための、エネルギー転移蛍光団により標識されたオリゴヌクレオチドラベルの設計及び合成
M13ユニバーサルプライマーから選択された、配列5′−GTTTTCCCAGTC−3′を有するデオキシオリゴヌクレオチド(12塩基の長さ)を、異なった距離により分離されたドナー−受容体螢光団対により合成した。特に、前記12ーマーは、C−5位置で第一アミンリンカーアームを有する、下記の5′ジメトキシトリチル−5−〔N−(トリフルオロアセチルアミノヘキシ)−3−アクリルイミド〕−2′−デオキシウリジン、3′−〔(2−シアノエチル)−(N,N−ジイソプロピル)〕−ホスホラミジット(Amino-Modifier C6dT)(構造体1)の使用により導入される修飾された塩基を含む:
代表的な例として、オリゴマー1に第2色素(TAM)を結合せしめる反応スキームが下記に示される:
Aで終結されるM13mp18の DNA配列決定フラグメントを、Sequenase2.0(USB)を用いて製造した。次の2種のアニーリング溶液を 600μlのバイアルに調製した:(1)10μlの反応緩衝液、40μlのM13mp18一本鎖 DNA及び6μlの FAM-3-ROX;(2)6μlの反応緩衝液、20μlのM13mp18一本鎖 DNA及び3μlのFAM-10-FAM。個々のバイアルを65℃で5分間加熱し、そして室温に30分間冷却し、そして次に、20分間、氷上に置き、短いプライマーが鋳型に完全にハイブリダイズしたことを確認した。3μLの DTT,20μlの ddA終結混合物及び12μLの希釈されたSequenase2.0を、氷上の個々のバイアルに添加した。
前述の発明は一層の理解のために例示的且つ例的にいくらか詳細に記載されて来たけれども、一定の変更及び修飾が本発明の範囲内で行なわれ得ることは明らかである。
ドナー蛍光団及び受容体蛍光団の対を担持する蛍光ラベルの組を含んで成る組成物が提供されており、前記組成物は、単一の波長でドナー蛍光団の効果的な励起及び異なった波長で前記個々の対における受容体蛍光団からの発光のために企画されている。異なったドナー蛍光団−受容体蛍光団対を有する異なった分子は、与えられた対におけるドナーと受容体との間の距離を変えることによって、分離条件下で実質的に同じ移動性を有するように変性され得る。特に、蛍光組成物は、核酸の配列決定においてラベルとして使用される。
Claims (1)
- 一本鎖核酸をコピーするためのプライマー及び特定のヌクレオチドで前記コピーに起因する鎖を終結するためのジデオキシヌクレオシドを用いて核酸配列を配列決定するための方法であって、
配列決定されるべき核酸フラグメントを、プライマーに結合する前記核酸フラグメントの5′側配列(プライマー結合配列)を含んで成るベクターでクローンニングし;
異なる反応容器において、前記プライマー、dNTP及び少量の異なった1種のジデオキシヌクレオチドの存在下で DNAポリメラーゼにより前記フラグメントをコピーし;そして
一本鎖 DNAフラグメントの得られる混合物を分離し、そしてゲル上に存在するバンドにより配列を決定することを含んで成り、
下記の点で改良されている配列決定方法:
ジデオキシヌクレオシドを用い、当該ジデオキシヌクレオシドは、
(1)ドナー蛍光団−受容体蛍光団対を含み、そして前記ドナー蛍光団から前記受容体蛍光団への効果的なエネルギーの転移を生じさせるものであり、
(2)前記個々のジデオキシヌクレオシドが実質的に同じ波長で吸光し、そして異なった波長で発光し;そして
(3)前記個々のジデオキシヌクレオシドが、当該ジデオキシヌクレオシド上の前記ドナー蛍光団−受容体蛍光団対のドナー蛍光団及びドナー蛍光団と受容体蛍光団との間の距離を変えることにより又は蛍光団自体を変えることにより前記分離において実質的に同じ移動性を有する、
ことを特徴とする。
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Application Number | Priority Date | Filing Date | Title |
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US08/189,924 US5654419A (en) | 1994-02-01 | 1994-02-01 | Fluorescent labels and their use in separations |
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JP52067995A Division JP3895369B2 (ja) | 1994-02-01 | 1995-01-30 | エネルギー転移連結の色素によりラベルされたプローブ |
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JP2007000151A true JP2007000151A (ja) | 2007-01-11 |
JP4602956B2 JP4602956B2 (ja) | 2010-12-22 |
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JP52067995A Expired - Lifetime JP3895369B2 (ja) | 1994-02-01 | 1995-01-30 | エネルギー転移連結の色素によりラベルされたプローブ |
JP2006257134A Expired - Lifetime JP4602956B2 (ja) | 1994-02-01 | 2006-09-22 | エネルギー転移連結の色素によりラベルされたプローブ |
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JP52067995A Expired - Lifetime JP3895369B2 (ja) | 1994-02-01 | 1995-01-30 | エネルギー転移連結の色素によりラベルされたプローブ |
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US (3) | US5654419A (ja) |
EP (1) | EP0743987B1 (ja) |
JP (2) | JP3895369B2 (ja) |
AT (1) | ATE236994T1 (ja) |
AU (1) | AU692230B2 (ja) |
CA (1) | CA2182516C (ja) |
DE (3) | DE29521620U1 (ja) |
ES (1) | ES2197193T3 (ja) |
WO (1) | WO1995021266A1 (ja) |
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AU1736795A (en) | 1995-08-21 |
US5688648A (en) | 1997-11-18 |
US5654419A (en) | 1997-08-05 |
DE19581489T1 (de) | 1997-01-02 |
JPH09508525A (ja) | 1997-09-02 |
JP4602956B2 (ja) | 2010-12-22 |
EP0743987A1 (en) | 1996-11-27 |
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