KR100781014B1 - 코발라민 분석 - Google Patents
코발라민 분석 Download PDFInfo
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- KR100781014B1 KR100781014B1 KR1020017003485A KR20017003485A KR100781014B1 KR 100781014 B1 KR100781014 B1 KR 100781014B1 KR 1020017003485 A KR1020017003485 A KR 1020017003485A KR 20017003485 A KR20017003485 A KR 20017003485A KR 100781014 B1 KR100781014 B1 KR 100781014B1
- Authority
- KR
- South Korea
- Prior art keywords
- ligand
- holo
- binding
- cobalamin
- sample
- Prior art date
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Abstract
Description
Claims (42)
- (i) 체액의 무세포 샘플을 트랜스코발라민 Ⅱ (TC Ⅱ) 및 합토코린의 아포 (apo)-형에 선택적으로 결합하는 고정 코발라민 또는 고정 코발라민의 유사체 또는 단편과 접촉시키는 단계;(ii) 이어서, 상기 샘플을 TC Ⅱ 또는 코발라민 결합 TC Ⅱ (홀로(holo) TC Ⅱ)에 대한 고정 또는 고정 가능한 특이성 결합 리간드와 접촉시키는 단계;(iii) 리간드 결합 분획을 리간드 비결합 분획으로부터 분리하는 단계;(iv) 리간드 결합 분획 중의 홀로 TC Ⅱ 또는 TC Ⅱ 결합 코발라민 함량을 측정하는 단계를 포함하고,상기 TC Ⅱ 결합 리간드가 109M-1 이상의 TC II의 결합에 대한 친화성 상수를 가지며, 상기 홀로 TC II 결합 리간드가 1010M-1이상의 홀로 TC II의 결합에 대한 친화성 상수를 갖는 것인,신체 샘플 중의 트랜스코발라민 Ⅱ 결합 코발라민의 측정을 위한 분석 방법.
- 제 1 항에 있어서, 상기 리간드 결합 분획 중의 홀로-TC Ⅱ의 농도가 상기 리간드 비결합 분획으로부터 리간드 결합 분획의 분리 후 3-배 이상 증가되는 것인 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 분석이 샘플 중 9 pM 농도의 홀로-TC Ⅱ를 검출할 수 있는 것인 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 특이성 결합 리간드가 폴리클로날 또는 모노클로날 항체, 항체 단편, 폴리펩티드, 올리고펩티드, 작은 유기 화학물질, 결합 화학 (combinatorial chemistry) 또는 파아지 디스플레이 라이브러리 (phage display library)로부터 선택된 특이성 결합제, DNA 또는 RNA의 특이성 결합 서열 또는 세포 표면 수용체를 포함하는 군으로부터 선택되는 것인 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 특이성 결합 리간드가 TC Ⅱ에 대하여 고도의 선택성 및 특이성을 나타내며 아포 또는 홀로형의 트랜스코발라민 I 및 III 또는 알부민에 대하여는 낮은 친화성을 나타내는 것인 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 단계 (iv)에서 코발라민 함량의 측정이 주위 매질의 온도 또는 pH를 변화시킴으로써 상기 코발라민을 홀로 TC Ⅱ 분자로부터 방출시킴으로써 수행되는 것인 분석 방법.
- 제 6 항에 있어서, 상기 방출된 코발라민을, 코발라민에 대한 고정 결합 파트너를 고정 결합 파트너에 결합하기 위해 분리 코발라민과 경쟁하는 표지 리간드의 존재하에 샘플 중의 해리된 코발라민과 접촉시킴으로써 수행되는 경쟁 분석에 의해 측정하는 것인 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 단계 (iv)에서, 고체 지지체 상에 고정된 TC Ⅱ 결합 리간드를 조사 샘플 및 비고정 리간드와 접촉시키고;상기 비고정 리간드가 홀로-TC Ⅱ에 대하여 특이성이고;상기 비고정 리간드에 결합된 상기 고정 리간드의 비율은 상기 샘플 중에 존재하는 홀로-TC Ⅱ의 양에 의존하고;상기 비고정 리간드는 결합 또는 비결합된 경우 직접 또는 간접적으로 검출 가능한 시그날을 발생시킬 수 있으며;결합 분획을 비결합 분획으로부터 분리하고;고정 리간드에 결합되거나, 비결합이고 용액 중의 비고정 리간드를 측정하는 것을 포함하는 분석 방법.
- 삭제
- 제 1 항 또는 제 2 항에 있어서, TC II 결합에 대한 친화성 상수가 1011M-1 보다 큰 분석 방법.
- 제 5 항에 있어서, 홀로-TC Ⅱ 또는 TC Ⅱ 결합 리간드와 HC(합토코린)의 교차 반응도가 0.1 내지 1%인 분석 방법.
- 제 5 항에 있어서, 홀로-TC Ⅱ 또는 TC Ⅱ 결합 리간드와 HC의 교차 반응도가 0 이상 0.1 % 미만인 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 단계 (iv)에서, 홀로-TC Ⅱ 복합체를 포함하는 상기 샘플을 고정 리간드에 결합한 표지 리간드가 결합된 고체 상과 접촉시키고, 상기 표지 리간드는 홀로 TC II와 동일한 고정 리간드 상의 결합 부위를 인식하는 것이며; 상기 샘플 중의 홀로-TC Ⅱ는 상기 결합 표지 리간드와 상기 결합 부위에 대하여 경쟁함으로써 시스템의 평형 후에 상기 고체 상으로부터 치환되고 용액 중에서 검출 가능한 표지 리간드의 양과 원래 샘플 중에 존재하는 홀로-TC Ⅱ의 양 사이에 직접적 비례 관계가 있으며; 상기 표지 리간드가 상기 고체 지지체에 결합되거나 결합 안된 표지 리간드의 양으로서 검출되는 것인 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 단계 (iv)에서, 상기 홀로-TC Ⅱ 함유 샘플을 그 위에 홀로-TC Ⅱ가 고정된 고체 상 및 표지 비고정 홀로-TC Ⅱ 특이성 리간드와 접촉시키며, 여기에서 샘플 중의 유리 홀로-TC Ⅱ 및 고정 홀로-TC Ⅱ가 표지 비고정 리간드와 결합하기 위해 경쟁하며; 상기 고체 상에 결합된 또는 용액 중에 잔류하는 표지 리간드의 측정으로 홀로-TC Ⅱ 농도의 측정이 가능한 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 단계 (iv)에서, 상기 홀로-TC Ⅱ 함유 샘플을 표지 홀로-TC Ⅱ 및 홀로-TC II에 대한 고정 리간드와 접촉시키고; 샘플 중의 상기 비표지 홀로-TC II 및 표지 홀로-TC Ⅱ는 고정 리간드에 결합하기 위하여 경쟁하고 평형에 다다른 후에, 고정 리간드에 결합된 표지 홀로-TC Ⅱ의 양은 샘플 중의 홀로-TC Ⅱ의 양에 간접적으로 비례하는 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 신체 샘플이 정액, 뇌척수액, 양수 또는 혈액 유래 샘플을 포함하는 군으로부터 선택되는 분석 방법.
- 제 16 항에 있어서, 상기 혈액 유래 샘플이 혈청 또는 혈장인 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 리간드 결합 분획이 상기 리간드 비결합 분획으로부터 침전, 원심분리, 여과 또는 크로마토그래피 방법에 의해 분리되는 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 상기 검출 가능한 리간드가 루미네센스 (luminescence), 화학 루미네센스 (chemiluminescence), 비색 평가, 형광, 방사능 또는 효소 활성에 의해 검출될 수 있는 시그날 형성 표지로 표지되는 분석 방법.
- 제 1 항 또는 제 2 항에 있어서, 홀로-TC Ⅱ 표준을 사용하여 분석 검정(assay calibration)을 실행하는 단계를 더 포함하는 분석 방법.
- 제 20 항에 있어서, 상기 홀로-TC II 표준이 인간 홀로-TC II, 천연 홀로-TC II 또는 재조합 홀로-TC Ⅱ인 분석 방법.
- TC Ⅱ 및 합토코린의 아포-형에 선택적으로 결합하는 고정 코발라민 또는 고정 코발라민의 유사체 또는 단편; 및고정 또는 고정 가능한 TC Ⅱ 또는 홀로-TC Ⅱ에 대한 특이성 결합 리간드를포함하는, 신체 샘플 중의 TC II 결합된 코발라민의 측정을 위한 제 1 항 또는 제 2 항에 따른 분석 방법에서 사용하기 위한 키트.
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 삭제
- 제 10 항에 있어서, 홀로-TC Ⅱ 또는 TC Ⅱ 결합 리간드와 HC의 교차 반응도가 0.1 내지 1%인 분석 방법.
- 제 1 항에 있어서, 홀로-TC Ⅱ 또는 TC Ⅱ 결합 리간드와 HC의 교차 반응도가 0 이상 0.1 % 미만인 분석 방법.
- 제 10 항에 있어서, 홀로-TC Ⅱ 또는 TC Ⅱ 결합 리간드와 HC의 교차 반응도가 0 이상 0.1 % 미만인 분석 방법.
- 제 22 항에 있어서, 그 농도를 알고 있는 홀로-TC Ⅱ를 갖는 용액 또는 홀로-TC Ⅱ 복합체 농도의 범위를 갖는 상기 용액의 셋트를 추가로 포함하는 제 1 항에 따른 분석 방법에서 사용하기 위한 키트.
- 제 22 항에 있어서, 홀로-TC Ⅱ로부터 코발라민을 방출시키는 방출제를 추가로 포함하는 제 1 항에 따른 분석 방법에서 사용하기 위한 키트.
- 제 22 항에 있어서, 표지 리간드를 추가로 포함하는 제 1 항에 따른 분석 방법에서 사용하기 위한 키트.
- 제 22 항에 있어서, 그 농도를 알고 있는 홀로-TC Ⅱ를 갖는 용액 또는 홀로-TC Ⅱ 복합체 농도의 범위를 갖는 상기 용액의 셋트를 추가로 포함하는 제 2 항에 따른 분석 방법에서 사용하기 위한 키트.
- 제 22 항에 있어서, 홀로-TC Ⅱ로부터 코발라민을 방출시키는 방출제를 추가로 포함하는 제 2 항에 따른 분석 방법에서 사용하기 위한 키트.
- 제 22 항에 있어서, 표지 리간드를 추가로 포함하는 제 2 항에 따른 분석 방법에서 사용하기 위한 키트.
- 제 8 항에 있어서, 상기 고정 리간드가 홀로 TC II 및 그의 경쟁자에 결합하고, 상기 비고정 리간드가 TC II에 결합하는 것인 분석 방법.
- 제 8 항에 있어서, 상기 고정 리간드가 홀로 TC II와 상기 비고정 리간드의 복합체에 결합하고, 상기 비고정 리간드가 TC II에 결합하는 것인 분석 방법.
- 제 8 항에 있어서, 상기 고정 리간드가 TC II와 상기 비고정 리간드의 복합체에 결합하고, 상기 비고정 리간드가 홀로 TC II에 결합하는 것인 분석 방법.
- 제 8 항에 있어서, 상기 고정 리간드가 TC II에 결합하고, 상기 비고정 리간드가 홀로 TC II와 상기 고정 리간드의 복합체에 결합하는 것인 분석 방법.
- 제 8 항에 있어서, 상기 고정 리간드가 홀로 TC II에 결합하고, 상기 비고정 리간드가 TC II와 상기 고정 리간드의 복합체에 결합하는 것인 분석 방법.
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GBGB9820473.8A GB9820473D0 (en) | 1998-09-18 | 1998-09-18 | Assay |
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GB0016460D0 (en) * | 2000-07-04 | 2000-08-23 | Axis Shield Asa | Assay |
GB0109925D0 (en) * | 2001-04-23 | 2001-06-13 | Axis Shield Asa | Method |
IN2015DN03908A (ko) | 2012-11-06 | 2015-10-02 | Hyundai Motor Co Ltd | |
CN104198598B (zh) * | 2014-07-15 | 2016-03-16 | 汤臣倍健股份有限公司 | 一种维生素b12的测定方法 |
CN106841017B (zh) * | 2017-01-22 | 2019-05-07 | 耐斯检测技术服务有限公司 | 一种评价辐照或热处理对钴胺素-蛋白结合体影响的方法 |
CN106693443A (zh) * | 2017-01-23 | 2017-05-24 | 北京美正生物科技有限公司 | 一种维生素b12适配体亲和柱及其制备方法和用途 |
JP7496411B2 (ja) * | 2019-08-09 | 2024-06-06 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレイテッド | 抗ブタtcn1モノクローナル抗体ならびにその作製方法および使用方法 |
CN113189252A (zh) * | 2021-04-19 | 2021-07-30 | 中国医学科学院北京协和医院 | 一种总钴胺素和氰钴胺的检测方法及其检测试剂盒和应用 |
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