JP5711216B2 - サンプル中のγ−ヒドロキシ酪酸(GHB)の濃度決定に適した方法、組成物およびキット - Google Patents
サンプル中のγ−ヒドロキシ酪酸(GHB)の濃度決定に適した方法、組成物およびキット Download PDFInfo
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- JP5711216B2 JP5711216B2 JP2012507692A JP2012507692A JP5711216B2 JP 5711216 B2 JP5711216 B2 JP 5711216B2 JP 2012507692 A JP2012507692 A JP 2012507692A JP 2012507692 A JP2012507692 A JP 2012507692A JP 5711216 B2 JP5711216 B2 JP 5711216B2
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Description
ラルストニア・ユートロファ(Ralstonia eutropha)、シュードモナス・プチダ(Pseudomonas putida)、および/またはボルデテラ・パラペルツッシス(Bordetella parapertussis)からの構築物が、出発原料として使用される。この方法によると、GHB−DH発現の最適化は3種類可能である:(1)大腸菌株(M15、BL−21およびXL1−ブルーMRF’)、(2)インダクタ濃度(IPTG)、および(3)インダクション用のインキュベーション温度(18℃〜37℃)。ラルストニア・ユートロファ、シュードモナス・プチダおよび/またはボルデテラ・パラペルツッシスからの配列を含むpQE−30UAベクターの構築物は、例えば、lac リプレッサーヘルパープラスミドpREP4を利用し、および利用しないで、XL1−ブルー中で形質転換される。正確な組み換えタンパクの発現は、抗His標識抗体を用いたSDS−PAGEおよびウエスタンブロットにより確認される。同時に、小スケールのIMACは、XL1−ブルー発現からGHB−DH凝集体の可溶化が行われる。その後、前記プラスミドは、選択された発現株のセットに再形質転換(retransform)される。
標的組み換えタンパクに対するα係数分泌シグナルを含むベクターpPICZalphaが、成長培地に付与される。目的の遺伝子の複数の複製物は、単一細胞中に統合されうる。多くの複製物は、ゼオシン濃度の増加により選択されうる。天然構築物からの前記GHB−DH配列(上記参照)は、His標識でラベルされていないベクターpPICZalpha A中に再クローン化される。ピキア・パストリスにおける形質転換は化学的方法で行われ、ゼオシン耐性により選択される。
本発明は、限定されないが、さらに以下の図によって説明される。図は典型的な特徴を表すものであり、例示目的のみのものであることが理解される。
Claims (18)
- (a)EDTAと共にシュウ酸を含む混合緩衝液を加えて希釈されたサンプルと、酸化型補因子を還元することによりγ−ヒドロキシ酪酸(GHB)をコハク酸セミアルデヒド(SSA)へ変換可能な酵素と、NADHへと還元される酸化型補因子であるNAD + と、の混合物をインキュベーションする工程、
(b)還元型補因子であるNADHの量を測定する工程、および
(c)前記還元型補因子であるNADHの測定量と前記サンプル中のGHBの濃度とを関連づける工程、を含み、
前記工程(a)の前記酵素がオキシドレダクターゼである、サンプル中のGHBの濃度の決定方法。 - 前記酵素がGHBデヒドロゲナーゼ、SSAレダクターゼ、グルクロン酸レダクターゼ
および/またはアルデヒドレダクターゼである、請求項1に記載の方法。 - 前記還元型補因子の測定波長が100nm〜650nmである、請求項1または2に記載の方法。
- 前記還元型補因子の測定波長が340nmである、請求項3に記載の方法。
- 前記混合物のインキュベーション温度が28〜50℃である、請求項1〜4のいずれか1項に記載の方法。
- 前記混合物のインキュベーション温度が37℃である、請求項5に記載の方法。
- 前記インキュベーション時間が1〜60分である、請求項1〜6のいずれか1項に記載の方法。
- 前記インキュベーション時間が8分である、請求項7に記載の方法。
- 前記混合物のpH値が8〜12である、請求項1〜8のいずれか1項に記載の方法。
- 前記pH値が10である、請求項9に記載の方法。
- (a)酸化型補因子を還元することによりGHBをコハク酸セミアルデヒド(SSA)へ変換可能な酵素であるオキシドレダクターゼ、
(b)NADHへと還元される酸化型補因子であるNAD + 、ならびに
(c)1〜100mMのシュウ酸、および0.1〜1.5mMのEDTAを含む緩衝液、
を成分として含むGHBサンプル分析用組成物。 - 前記酵素がGHBデヒドロゲナーゼである、請求項11に記載の組成物。
- 前記酸化型補因子が0.1〜10mMのNAD+である、請求項11または12に記載の組成物。
- 請求項1〜10のいずれか1項に記載の方法を行うのに適したキット。
- 請求項11〜13のいずれか1項に記載の組成物を含む、請求項14に記載のキット。
- マイクロタイタープレートにおける用途への請求項1〜10のいずれか1項に記載の方法の使用。
- オートアナライザーにおける用途への請求項1〜10のいずれか1項に記載の方法の使用。
- 前記工程(a)の前記酵素が、合成的に製造された遺伝子構築物から得られたものである、請求項1〜10のいずれか1項に記載の方法。
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EP09005884.3 | 2009-04-28 | ||
EP09005884.3A EP2253711B1 (en) | 2009-04-28 | 2009-04-28 | Methods, compositions and a kit suitable for determining the concentration of gamma-hydroxy butyric acid (GHB) in a sample |
PCT/EP2010/055436 WO2010124999A1 (en) | 2009-04-28 | 2010-04-23 | Methods, compositions and a kit suitable for determining the concentration of gamma-hydroxy butyric acid (ghb) in a sample |
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EP (1) | EP2253711B1 (ja) |
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BR112013014100A2 (pt) * | 2010-12-06 | 2016-08-02 | Univ Ramot | método para determinar a presença/ausência de uma droga em um meio líquido, e, dispositivo para determinar a presença de uma droga em um meio líquido |
GB201116420D0 (en) * | 2011-09-23 | 2011-11-02 | Univ Strathclyde | GHB detection |
CN104111253A (zh) * | 2014-06-20 | 2014-10-22 | 武汉高丰生物科技有限公司 | 一种抗抗坏血酸和色素干扰的4-羟基丁酸检测试纸的制备方法 |
CN104713874B (zh) * | 2015-03-05 | 2016-08-31 | 杭州欣叶生物科技有限公司 | 乳腺癌尿液检测试剂和检测试剂盒及其制备和检测方法 |
CN104897667B (zh) * | 2015-06-19 | 2017-10-03 | 公安部物证鉴定中心 | Smith试剂在检测液体检材中GHB中的应用 |
CN107014939B (zh) * | 2017-02-27 | 2018-06-08 | 南京市公安局刑事侦查局 | 离子排斥-离子交换柱切换联用测定尿液中的γ-羟基丁酸的方法 |
CN111208247A (zh) * | 2020-01-08 | 2020-05-29 | 浙江工业大学 | 在线热辅助甲基化-气相色谱质谱法测定人体毛发中γ-羟基丁酸含量的方法 |
KR20210091996A (ko) | 2020-01-15 | 2021-07-23 | 금오공과대학교 산학협력단 | 감마-히드록시뷰티릭산 감지 물질이 도포된 섬유를 포함하는 감지키트 및 이의 제조방법 |
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US6153147A (en) * | 1998-10-06 | 2000-11-28 | Craig; James J. | Beverage analysis sample |
US20050233459A1 (en) * | 2003-11-26 | 2005-10-20 | Melker Richard J | Marker detection method and apparatus to monitor drug compliance |
US20010046710A1 (en) * | 2000-02-04 | 2001-11-29 | Cutler Charlyne E. | Narcotics detector test strips for a beverage |
US6617123B1 (en) * | 2000-06-29 | 2003-09-09 | Jack V. Smith | Method for detection of 4-hydroxybutyric acid and its precursor(s) in fluids |
US6703216B2 (en) * | 2002-03-14 | 2004-03-09 | The Regents Of The University Of California | Methods, compositions and apparatuses for detection of gamma-hydroxybutyric acid (GHB) |
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Free format text: JAPANESE INTERMEDIATE CODE: R250 |
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |