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RU2229469C1 - Butyrylcholine chloride highly labeled with tritium - Google Patents

Butyrylcholine chloride highly labeled with tritium Download PDF

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RU2229469C1
RU2229469C1 RU2002126718/04A RU2002126718A RU2229469C1 RU 2229469 C1 RU2229469 C1 RU 2229469C1 RU 2002126718/04 A RU2002126718/04 A RU 2002126718/04A RU 2002126718 A RU2002126718 A RU 2002126718A RU 2229469 C1 RU2229469 C1 RU 2229469C1
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tritium
labeled
butyrylcholine chloride
butyrylcholine
highly labeled
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RU2002126718/04A
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RU2002126718A (en
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В.П. Шевченко (RU)
В.П. Шевченко
соедов Н.Ф. М (RU)
Н.Ф. Мясоедов
И.Ю. Нагаев (RU)
И.Ю. Нагаев
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Институт молекулярной генетики РАН
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Abstract

FIELD: organic chemistry, labeled compound, biochemistry. SUBSTANCE: invention relates to a novel highly labeled butyrylcholine chloride of the formula: [3H]-C3H7-COO-CH2-CH2- N+(CH3)3Cl- that is analog of butyrylcholine chloride and can be used in analytical chemistry, bioorganic chemistry, biochemistry and applied medicine, in particular, for assay of choline esterase activity. EFFECT: valuable properties of compound. 1 ex

Description

Изобретение относится к области органической химии и может найти применение в аналитической химии, биоорганической химии, биохимии и прикладной медицине.The invention relates to the field of organic chemistry and can find application in analytical chemistry, bioorganic chemistry, biochemistry and applied medicine.

Известен бутирилхолинхлорид формулы I:Known butyrylcholine chloride of the formula I:

Figure 00000001
Figure 00000001

Данное соединение используется для определения активности холинэстеразы Sumner, Somers, Chemistry and Methods of Enzymes (New York, 1947), Mendel, Mundell, Biochem. J. 37, 64 (1943) Davies, Green, Advan. Enzymol 20, 283 (1958). The Merck Index 1999 N 2264.This compound is used to determine the activity of cholinesterase Sumner, Somers, Chemistry and Methods of Enzymes (New York, 1947), Mendel, Mundell, Biochem. J. 37, 64 (1943) Davies, Green, Advan. Enzymol 20, 283 (1958). The Merck Index 1999 N 2264.

Ряд методов исследования физиологически активных соединений требует наличия их меченых аналогов.A number of methods for studying physiologically active compounds require the presence of their labeled analogues.

Однако меченные тритием аналоги бутирилхолинхлорида не описаны.However, tritium-labeled butyrylcholine chloride analogues are not described.

Известно, что замена атомов соединений на их меченые аналоги не приводит к изменению каких-либо свойств исходного соединения (Evans Е.А. - Tritium and its compounds London Butterworths, 1947, p.48).It is known that the replacement of atoms of compounds with their labeled analogues does not lead to a change in any properties of the starting compound (Evans E.A. - Tritium and its compounds London Butterworths, 1947, p. 48).

Техническим результатом, достигаемым настоящим изобретением, является расширение ассортимента меченых аналогов физиологически активных веществ.The technical result achieved by the present invention is to expand the range of labeled analogues of physiologically active substances.

Достигается указанный технический результат получением нового меченого физиологически активного соединения - высокомеченного тритием бутирилхолинхлорида формулы II:This technical result is achieved by obtaining a new labeled physiologically active compound - highly labeled with tritium butyrylcholine chloride of the formula II:

Figure 00000002
Figure 00000002

Ниже приведен пример реализации изобретения.The following is an example implementation of the invention.

Пример 1Example 1

В реакционную ампулу помещали 2 мг бутирилхолинхлорида, нанесенного на 20 мг 5% Pt/C. Затем ампулу вакуумировали до давления 0,1 Па, заполняли газообразным тритием до давления 400 гПа и выдерживали при температуре 180°С 10 мин. Избыточный тритий удаляли вакуумированием. После охлаждения продукты реакции растворяли в 2 мл метанола с 10 мкл концентрированной соляной кислоты, катализатор отфильтровывали, а фильтраты упаривали несколько раз в виде раствора в метаноле (3×3 мл) для удаления лабильного трития. Остаток разделили на три зоны, используя бумажную хроматографию. Зона, содержащая бутирилхолинхлорид, включала 66% общей метки. Окончательную очистку проводили методом ВЭЖХ. Из реакционной смеси выделен меченый бутирилхолинхлорид с выходом 16% и молярной радиоактивностью - 6,5 Ки/ммоль, радиохимической чистотой - 98-99%.2 mg of butyrylcholine chloride, applied to 20 mg of 5% Pt / C, were placed in the reaction vial. Then the ampoule was evacuated to a pressure of 0.1 Pa, filled with gaseous tritium to a pressure of 400 hPa and kept at a temperature of 180 ° C for 10 minutes. Excess tritium was removed by vacuum. After cooling, the reaction products were dissolved in 2 ml of methanol with 10 μl of concentrated hydrochloric acid, the catalyst was filtered off, and the filtrates were evaporated several times as a solution in methanol (3 × 3 ml) to remove labile tritium. The residue was divided into three zones using paper chromatography. The butyrylcholine chloride zone included 66% of the total label. Final purification was carried out by HPLC. Labeled butyrylcholine chloride was isolated from the reaction mixture in 16% yield and 6.5 Ci / mmol molar radioactivity, 98-99% radiochemical purity.

Бумажная хроматография. На бумаге Whatman ЗММ, в системе бутанол-этанол-уксусная кислота-вода (8:2:1:3), Rf 0,67.Paper chromatography. On Whatman ZMM paper, in the system butanol-ethanol-acetic acid-water (8: 2: 1: 3), R f 0.67.

ВЭЖХ бутирилхолинхлорида проводили на колонке Kromasil 100 C18, 7 мкм, 4×150 мм, в системе метанол-вода-гептафтормасляная кислота (30:70:0,1), скорость элюента - 1,0 мл/мин, время удерживания – 8,76 мин.HPLC of butyrylcholine chloride was carried out on a Kromasil 100 C 18 , 7 μm, 4 × 150 mm column, in the methanol-water-heptafluorobutyric acid system (30: 70: 0.1), the eluent speed was 1.0 ml / min, and the retention time was 8 , 76 minutes

Для приема и обработки хроматографических данных использовался программно-аппаратный комплекс “МультиХром” (ЗАО “Амперсенд”, Россия) на базе IВМ PC/AT. Радиоактивность измеряли на сцинтилляционном счетчике с эффективностью регистрации трития 30% в диоксановом сцинтилляторе.To receive and process chromatographic data, the MultiKhrom software and hardware complex (Ampersend CJSC, Russia) was used on the basis of IBM PC / AT. Radioactivity was measured on a scintillation counter with a tritium detection efficiency of 30% in a dioxane scintillator.

Таким образом, получено новое высокомеченное тритием физиологически активное соединение.Thus, a new physiologically active compound highly labeled with tritium was obtained.

Claims (1)

Высокомеченный тритием бутирилхолинхлорид формулыHighly labeled tritium butyrylcholine chloride of the formula [3H]C3H7-COO-CH2CH2-N+(CH3)3 Сl-.[ 3 H] C 3 H 7 —COO — CH 2 CH 2 —N + (CH 3 ) 3 Cl - .
RU2002126718/04A 2002-10-08 2002-10-08 Butyrylcholine chloride highly labeled with tritium RU2229469C1 (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU1184233A3 (en) * 1983-04-15 1994-03-15 Институт молекулярной генетики РАН Method of obtaining organic compound marked by tritium
US5563014A (en) * 1995-05-15 1996-10-08 Xerox Corporation Migration imaging members

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU1184233A3 (en) * 1983-04-15 1994-03-15 Институт молекулярной генетики РАН Method of obtaining organic compound marked by tritium
US5563014A (en) * 1995-05-15 1996-10-08 Xerox Corporation Migration imaging members

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