JPH09506858A - ヌクレオシド誘導体、該ヌクレオシド誘導体の製造方法、および該誘導体の特異的ポリクローナルおよびモノクローナル抗体 - Google Patents
ヌクレオシド誘導体、該ヌクレオシド誘導体の製造方法、および該誘導体の特異的ポリクローナルおよびモノクローナル抗体Info
- Publication number
- JPH09506858A JPH09506858A JP7509021A JP50902195A JPH09506858A JP H09506858 A JPH09506858 A JP H09506858A JP 7509021 A JP7509021 A JP 7509021A JP 50902195 A JP50902195 A JP 50902195A JP H09506858 A JPH09506858 A JP H09506858A
- Authority
- JP
- Japan
- Prior art keywords
- amino
- oxo
- nucleoside derivative
- guanine
- protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 claims abstract description 58
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- 230000000694 effects Effects 0.000 description 2
- 210000000267 erythroid cell Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 239000005350 fused silica glass Substances 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000015788 innate immune response Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000005865 ionizing radiation Effects 0.000 description 2
- DRAVOWXCEBXPTN-UHFFFAOYSA-N isoguanine Chemical compound NC1=NC(=O)NC2=C1NC=N2 DRAVOWXCEBXPTN-UHFFFAOYSA-N 0.000 description 2
- 150000002605 large molecules Chemical class 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 150000003014 phosphoric acid esters Chemical group 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000002336 ribonucleotide Substances 0.000 description 2
- 125000002652 ribonucleotide group Chemical group 0.000 description 2
- 229910052895 riebeckite Inorganic materials 0.000 description 2
- 229910001923 silver oxide Inorganic materials 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N titanium dioxide Inorganic materials O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 230000002485 urinary effect Effects 0.000 description 2
- 210000002700 urine Anatomy 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- NHMYNFQKSUABCL-UHFFFAOYSA-N 2-[2-(4-amino-5-hydroxy-2-oxopyrimidin-1-yl)-6-(hydroxymethyl)morpholin-4-yl]acetic acid Chemical compound C1=C(O)C(N)=NC(=O)N1C1OC(CO)CN(CC(O)=O)C1 NHMYNFQKSUABCL-UHFFFAOYSA-N 0.000 description 1
- VKIGAWAEXPTIOL-UHFFFAOYSA-N 2-hydroxyhexanenitrile Chemical compound CCCCC(O)C#N VKIGAWAEXPTIOL-UHFFFAOYSA-N 0.000 description 1
- CLGFIVUFZRGQRP-UHFFFAOYSA-N 7,8-dihydro-8-oxoguanine Chemical compound O=C1NC(N)=NC2=C1NC(=O)N2 CLGFIVUFZRGQRP-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101100284769 Drosophila melanogaster hemo gene Proteins 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CJPQIRJHIZUAQP-MRXNPFEDSA-N benalaxyl-M Chemical compound CC=1C=CC=C(C)C=1N([C@H](C)C(=O)OC)C(=O)CC1=CC=CC=C1 CJPQIRJHIZUAQP-MRXNPFEDSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 102220201851 rs143406017 Human genes 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Saccharide Compounds (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 以下の化学式: (式中、R1は、Hまたは直鎖のモノ−、ジ−、またはトリ−リン酸を示し、 R2は、ヒドロキシル基、アルキル基、アリール基、フリーアミノ部位を取り込 む蛋白質、アミノアルキル=ポリスチレン、またはアルキルアミン鎖でグラフト したシリカを示し、R3は、ウラシル、チミン、シトシン、グアニン、またはア デニンから選択された置換塩基を示す) で表わされるヌクレオシド誘導体。 2. R3が、(5−ヒドロキシシトシン)−1−イル、(5−ヒドロキ シヒダントイン)−1−イル、−NH−CO−NH−CO−NH2、(5−ヒド ロキシウラシル)−1−イル、(5−ホルミルウラシル)−1−イル、(5−ヒ ドロキシメチルウラシル)−1−イル、−NH−CHO、(5,6−ジヒドロキ シチミン)−1−イル、(5,6−ジヒドロチミン)−1−イル、(5,6−ジ ヒドロ−5−ヒドロキシチミン)−1−イル、アデニン−Nl−オキシド、(8 −オキソ−7,8−ジヒドロアデニン)−9−イル、[(6−アミノ−5−ホル ミルアミノ−ピリミジン)−4−イル]アミノ、(8−オキソ−7,8−ジヒド ログアニン)−9−イル、[(2−アミノ−6−オキソ−5−ホルミルアミノピ リミジン)−4−イル]−アミノ、(4,8−ジヒドロ−4−ヒドロキシ−8− オキソ−グアニン)−9−イル、または[(2,2−ジアミノ−オキサゾール− 4オン)−5−イル]アミノから選択される、請求項1に記載のヌクレオシド誘 導体。 3. R2が、メチル化ボビン血清アルブミン、ターキーまたはチキンの 卵アルブミン、またはヘモシアニンから選択された蛋白質である、請求項1また は2に記載のヌクレオシド誘導体。 4. 以下の化学式: (式中、R1は、Hまたは直鎖のモノ−、ジ−、またはトリ−リン酸を示し、 R6は、ヒドロキシル基、アルキル基、またはアリール基を示し、R3は、クラシ ル、チミン、シトシン、グアニン、またはアデニンから選択された置換塩基を示 す) で表わされるヌクレオシド誘導体の製造方法であって、 以下の化学式: (式中、R1およびR6は、前記と同様の意味を示し、R4は、ウラシル、チミ ン、シトシン、グアニン、またはアデニンから選択された置換塩基を示す) で表わされるヌクレオシド誘導体と置換基を反応させることからなる、式(II )で表わされるヌクレオシド誘導体の製造方法。 5. 前記置換基が、オゾン、過酸化水素、コリジンと組み合わせたブロ ミン、Ag2Oおよびブロミン、過マンガン酸カリウム、4酸化オスミウム、メタ ナール、またはAlLiH4から選択された薬剤である、請求項4に記載のヌクレ オシド誘導体の製造方法。 6. 前記置換基が、光化学、任意の酸素の存在下のイオン化光線、接触 水素化、またはブロミンおよび水による処理とそれに続く水素化分解から選択さ れた処理である、請求項4に記載のヌクレオシド誘導体の製造方法。 7. R3が、(5−ヒドロキシシトシン)−1−イル、(5−ヒドロキ シヒダントイン)−1−イル、−NH−CO−NH−CO−NH2、(5−ヒド ロキシウラシル)−1−イル、(5−ホルミルウラシル)−1−イル、(5−ヒ ドロキシメチルウラシル)−1−イル、−NH−CHO、(5,6−ジヒドロ− 5,6−ジヒドロキシチミン)−1−イル、(5,6−ジヒドロチミン)−1− イル、(5,6−ジヒドロ−5−ヒドロキシチミン)−1−イル、アデニン−N l−オキシド、(8−オキソ−7,8−ジヒドロアデニン)−9−イル、[(6 −アミノ−5−ホルミルアミノ−ピリミジン)−4−イル]アミノ、(8−オキ ソ−7,8−ジヒドログアニン)−9−イル、[(2−アミノ−6−オキソ−5 −ホルミルアミノピリミジン)−4−イル]−アミノ、(4,8−ジヒドロ−4 −ヒドロキシ−8−オキソ−グアニン)−9−イル、または[(2,2−ジアミ ノ−オキサゾール−4−オン)−5−イル]アミノから選択される、請求項4に 記載のヌクレオシド誘導体の製造方法。 8. 以下の化学式: (式中、R1は、Hまたは直鎖のモノ−、ジ−、またはトリ−リン酸を示し、 R5は、蛋白質、アルキルポリスチレン、またはアルキル鎖でグラフトしたシリ カを示し、R3は、ウラシル、チミン、シトシン、グアニン、またはアデニンか ら選択された置換塩基を示す) で表わされるヌクレオシド誘導体の製造方法であって、該方法は、NH2−R5 タイプの化合物(式中、R5は、上記と同様の意味をしめす)を、以下の化学式 : (式中、R1およびR3は、前記と同様の意味を示す) で表わされるヌクレオシド誘導体と反応させることからなる、式(V)で表わ されるヌクレオシド誘導体の製造方法。 9. R3が、(5−ヒドロキシシトシン)−1−イル、(5−ヒドロキ シヒダントイン)−1−イル、−NH−CO−NH−CO−NH2、(5−ヒド ロキシウラシル)−1−イル、(5−ホルミルウラシル)−1−イル、(5−ヒ ドロキシメチルウラシル)−1−イル、−NH−CHO、(5,6−ジヒドロ− 5,6−ジヒドロキシチミン)−1−イル、(5,6−ジヒドロチミン)−1− イル、(5,6−シヒドロ−5−ヒドロキシチミン)−1−イル、アデニン−N l−オキシド、(8−オキソ−7,8−ジヒドロアデニン)−9−イル、[(6 −アミノ−5−ホルミルアミノ−ピリミジン)−4−イル]アミノ、(8−オキ ソ−7,8−ジヒドログアニン)−9−イル、[(2−アミノ−6−オキソ−5 −ホルミルアミノピリミジン)−4−イル]−アミノ、(4,8−ジヒドロ−4 −ヒドロキシ−8−オキソ−グアニン)−9−イル、または[(2,2−ジアミ ノ−オキサゾール−4−オン)−5−イル]−アミノから選択される、請求項8 に記載のヌクレオシド誘導体の製造方法。 10. 以下の化学式: (式中、R1は、Hまたは直鎖のモノ−、ジ−、またはトリ−リン酸を示し、 R3は、ウラシル、チミン、シトシン、グアニン、またはアデニンから選択され た置換核塩基を示し、R5は、哺乳類由来の蛋白質ではない) で表わされる抗原を用いた適当な哺乳類の免疫化によって得られることを特徴 とする、ヌクレオシドから逆誘導された(anti−derived)ポリクローナル抗体 。 11. R5が、メチル化ボビン血清アルブミン、ターキーまたはチキン の卵アルブミン、またはヘモシアニンから選択された蛋白質である、請求項10 に記載のポリクローナル抗体。 12. R3が、(5−ヒドロキシシトシン)−1−イル、(5−ヒドロ キシヒダントイン)−1−イル、−NH−CO−NH−CO−NH2、(5−ヒ ドロキシウラシル)−1−イル、(5−ホルミルウラシル)−1−イル、(5− ヒドロキシメチルウラシル)−1−イル、−NH−CHO、(5,6−ジヒドロ −5,6−ジヒドロキシチミン)−1−イル、(5,6−ジヒドロチミン)−1 −イル、(5,6−ジヒドロ−5−ヒドロキシチミン)−1−イル、アデニン− Nl−オキシド、(8−オキソ−7,8−ジヒドロアデニン)−9−イル、[( 6−アミノ−5−ホルミルアミノ−ピリミジン)−4−イル]アミノ、(8−オ キソ−7,8−ジヒドログアニン)−9−イル、[(2−アミノ−6−オキソ− 5−ホルミルアミノピリミジン)−4−イル]−アミノ、(4,8−ジヒドロ− 4−ヒドロキシ−8−オキソ−グアニン)−9−イル、または[(2,2−ジア ミノ−オキ サゾール−4−オン)−5−イル]−アミノから選択される、請求項10に記載 のポリクローナル抗体。 13. 以下の化学式: (式中、R1は、Hまたは直鎖のモノ−、ジ−またはトリ−リン酸を示し、R3 は、ウラシル、チミン、シトシン、グアニン、またはアデニンから選択された置 換核塩基を示し、R5は、マウス由来の蛋白質ではない) で表わされる抗原によって免疫化されたマウスのひ臓細胞を用いた哺乳類のミ エローマ細胞の融合によって得られることを特徴とする、ヌクレオシドから逆誘 導された(anti−derived)モノクローナル抗体。 14. R5が、メチル化ボビン血清アルブミン、ターキーまたはチキン の卵アルブミン、またはヘモシアニンから選択された蛋白質である、請求項13 に記載のモノクローナル抗体。 15. R3が、(5−ヒドロキシシトシン)−1−イル、(5−ヒドロ キシヒダントイン)−1−イル、−NH−CO−NH−CO−NH2、(5−ヒ ドロキシウラシル)−1−イル、(5−ホルミルウラシル)−1−イル、(5− ヒドロキシメチルウラシル)−1−イル、−NH−CHO、(5,6−ジヒドロ −5,6−ジヒドロキシチミン)−1−イル、(5,6−ジヒドロチミン)−1 −イル、(5,6−ジヒドロ−5−ヒドロキシチミン)−1−イル、アデニン− Nl−オキシド、(8−オキソ−7,8−ジヒドロアデニン)−9−イル、[( 6−アミノ−5−ホルミルアミノ−ピリミジン)−4−イル]アミノ、(8−オ キソ−7, 8−ジヒドログアニン)−9−イル、[(2−アミノ−6−オキソ−5−ホルミ ルアミノピリミジン)−4−イル]−アミノ、(4,8−ジヒドロ−4−ヒドロ キシ−8−オキソ−グアニン)−9−イル、または[(2,2−ジアミノ−オキ サゾール−4−オン)−5−イル]−アミノから選択される、請求項13に記載 のモノクローナル抗体。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9310864A FR2710068B1 (fr) | 1993-09-13 | 1993-09-13 | Dérivés de nucléosides, procédés de fabrication de ces dérivés de nucléosides et anticorps polyclonaux et monoclonaux spécifiques de ces dérivés. |
FR93/10864 | 1993-09-13 | ||
PCT/FR1994/001070 WO1995007907A1 (fr) | 1993-09-13 | 1994-09-12 | Derives de nucleosides, procedes de fabrication de ces derives de nucleosides et anticorps polyclonaux et monoclonaux specifiques de ces derives |
Publications (2)
Publication Number | Publication Date |
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JPH09506858A true JPH09506858A (ja) | 1997-07-08 |
JP3854632B2 JP3854632B2 (ja) | 2006-12-06 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP50902195A Expired - Fee Related JP3854632B2 (ja) | 1993-09-13 | 1994-09-12 | ヌクレオシド誘導体、該ヌクレオシド誘導体の製造方法、および該誘導体の特異的ポリクローナルおよびモノクローナル抗体 |
Country Status (6)
Country | Link |
---|---|
US (1) | US5721341A (ja) |
EP (1) | EP0719265B1 (ja) |
JP (1) | JP3854632B2 (ja) |
DE (1) | DE69415030T2 (ja) |
FR (1) | FR2710068B1 (ja) |
WO (1) | WO1995007907A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU7113696A (en) * | 1995-09-19 | 1997-04-09 | Cytochem, Inc. | Detection and quantitation of 8-oh-adenine using monoclonal antibodies |
FR2790004B1 (fr) * | 1999-02-22 | 2002-11-29 | Commissariat Energie Atomique | Procede de fabrication de morpholino-nucleotides, et utilisation de ceux-ci pour l'analyse et le marquage de sequences d'acides nucleiques |
FR2790005B1 (fr) | 1999-02-22 | 2004-01-30 | Commissariat Energie Atomique | Procede de fabrication de morpholino-nucleotides, et utilisation de ceux-ci pour l'analyse et le marquage de sequences d'acides nucleiques |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US4515781A (en) * | 1983-02-23 | 1985-05-07 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | 2',5'-Riboadenylate-morpholinoadenylate nucleotides |
WO1991018898A1 (fr) * | 1990-06-01 | 1991-12-12 | Nippon Shinyaku Co., Ltd. | Homologue d'acide nucleique |
JPH06505704A (ja) * | 1990-09-20 | 1994-06-30 | ギリアド サイエンシズ,インコーポレイテッド | 改変ヌクレオシド間結合 |
US5382580A (en) * | 1994-05-27 | 1995-01-17 | The Scripps Research Institute | N9 morpholino derivatives of 7,8-disubstituted guanines |
-
1993
- 1993-09-13 FR FR9310864A patent/FR2710068B1/fr not_active Expired - Fee Related
-
1994
- 1994-09-12 EP EP94926977A patent/EP0719265B1/fr not_active Expired - Lifetime
- 1994-09-12 WO PCT/FR1994/001070 patent/WO1995007907A1/fr active IP Right Grant
- 1994-09-12 JP JP50902195A patent/JP3854632B2/ja not_active Expired - Fee Related
- 1994-09-12 US US08/605,134 patent/US5721341A/en not_active Expired - Lifetime
- 1994-09-12 DE DE69415030T patent/DE69415030T2/de not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
FR2710068A1 (fr) | 1995-03-24 |
EP0719265B1 (fr) | 1998-12-02 |
FR2710068B1 (fr) | 1995-10-20 |
EP0719265A1 (fr) | 1996-07-03 |
DE69415030D1 (de) | 1999-01-14 |
JP3854632B2 (ja) | 2006-12-06 |
US5721341A (en) | 1998-02-24 |
WO1995007907A1 (fr) | 1995-03-23 |
DE69415030T2 (de) | 1999-06-10 |
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