JP2017518261A - 反応性標識化合物およびその使用 - Google Patents
反応性標識化合物およびその使用 Download PDFInfo
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- JP2017518261A JP2017518261A JP2016558730A JP2016558730A JP2017518261A JP 2017518261 A JP2017518261 A JP 2017518261A JP 2016558730 A JP2016558730 A JP 2016558730A JP 2016558730 A JP2016558730 A JP 2016558730A JP 2017518261 A JP2017518261 A JP 2017518261A
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- Prior art keywords
- optionally substituted
- alkyl
- compound
- aryl
- certain embodiments
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 140
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- 125000003118 aryl group Chemical group 0.000 claims description 97
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- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 1
- BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
- FAQJJMHZNSSFSM-UHFFFAOYSA-N phenylglyoxylic acid Chemical compound OC(=O)C(=O)C1=CC=CC=C1 FAQJJMHZNSSFSM-UHFFFAOYSA-N 0.000 description 1
- ABOYDMHGKWRPFD-UHFFFAOYSA-N phenylmethanesulfonamide Chemical compound NS(=O)(=O)CC1=CC=CC=C1 ABOYDMHGKWRPFD-UHFFFAOYSA-N 0.000 description 1
- NIXKBAZVOQAHGC-UHFFFAOYSA-N phenylmethanesulfonic acid Chemical compound OS(=O)(=O)CC1=CC=CC=C1 NIXKBAZVOQAHGC-UHFFFAOYSA-N 0.000 description 1
- AFDMODCXODAXLC-UHFFFAOYSA-N phenylmethanimine Chemical compound N=CC1=CC=CC=C1 AFDMODCXODAXLC-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 1
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- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
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- FLCPORVHXQFBHT-UHFFFAOYSA-N quinolin-8-yl carbamate Chemical compound C1=CN=C2C(OC(=O)N)=CC=CC2=C1 FLCPORVHXQFBHT-UHFFFAOYSA-N 0.000 description 1
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- BDEZGPKAMAVGBE-UHFFFAOYSA-N s-(3-nitropyridin-2-yl)thiohydroxylamine Chemical compound NSC1=NC=CC=C1[N+]([O-])=O BDEZGPKAMAVGBE-UHFFFAOYSA-N 0.000 description 1
- DAXSYWBYJZACTA-UHFFFAOYSA-N s-(4-methoxy-2-nitrophenyl)thiohydroxylamine Chemical compound COC1=CC=C(SN)C([N+]([O-])=O)=C1 DAXSYWBYJZACTA-UHFFFAOYSA-N 0.000 description 1
- LOFZYSZWOLKUGE-UHFFFAOYSA-N s-benzyl carbamothioate Chemical compound NC(=O)SCC1=CC=CC=C1 LOFZYSZWOLKUGE-UHFFFAOYSA-N 0.000 description 1
- MAGSSGQAJNNDLU-UHFFFAOYSA-N s-phenylthiohydroxylamine Chemical compound NSC1=CC=CC=C1 MAGSSGQAJNNDLU-UHFFFAOYSA-N 0.000 description 1
- PIDYQAYNSQSDQY-UHFFFAOYSA-N s-tritylthiohydroxylamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(SN)C1=CC=CC=C1 PIDYQAYNSQSDQY-UHFFFAOYSA-N 0.000 description 1
- BPELEZSCHIEMAE-UHFFFAOYSA-N salicylaldehyde imine Chemical compound OC1=CC=CC=C1C=N BPELEZSCHIEMAE-UHFFFAOYSA-N 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 239000012363 selectfluor Substances 0.000 description 1
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- 238000011896 sensitive detection Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
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- 230000009450 sialylation Effects 0.000 description 1
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- 150000003384 small molecules Chemical class 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- PVGBHEUCHKGFQP-UHFFFAOYSA-N sodium;n-[5-amino-2-(4-aminophenyl)sulfonylphenyl]sulfonylacetamide Chemical compound [Na+].CC(=O)NS(=O)(=O)C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 PVGBHEUCHKGFQP-UHFFFAOYSA-N 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
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- 230000003595 spectral effect Effects 0.000 description 1
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- 210000002784 stomach Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 125000000565 sulfonamide group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- XKXIQBVKMABYQJ-UHFFFAOYSA-M tert-butyl carbonate Chemical compound CC(C)(C)OC([O-])=O XKXIQBVKMABYQJ-UHFFFAOYSA-M 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 150000003555 thioacetals Chemical class 0.000 description 1
- 230000008448 thought Effects 0.000 description 1
- UIERETOOQGIECD-ONEGZZNKSA-N tiglic acid Chemical compound C\C=C(/C)C(O)=O UIERETOOQGIECD-ONEGZZNKSA-N 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- 108010004486 trans-sialidase Proteins 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 description 1
- IARSSOVWSJAVSZ-UHFFFAOYSA-N tris(dimethylamino)sulfanium Chemical compound CN(C)[S+](N(C)C)N(C)C IARSSOVWSJAVSZ-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000000107 tumor biomarker Substances 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 150000008135 α-glycosides Chemical class 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/14—Nitrogen atoms not forming part of a nitro radical
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/027—Organoboranes and organoborohydrides
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
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- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
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- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/924—Hydrolases (3) acting on glycosyl compounds (3.2)
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- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2458/00—Labels used in chemical analysis of biological material
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Abstract
Description
本開示は、2014年3月27日に出願された米国特許仮出願第61/971,313号の優先権の利益を主張する。その内容は、本明細書において参考として援用される。
本開示は、シクロオクチンが縮合した蛍光発生プローブのトリアゾール形成、アジド−BODIPY化合物、ならびにアルキン含有またはアジド含有生体分子の診断およびイメージングのための蛍光で切断されるプローブの分野に関する。本開示は、アジド−アルキン環化付加(AAC)による蛍光増強戦略に関する。
いくつかのアジド−BODIPY誘導体が、CuAAC反応による蛍光標識化のために開発されてきた。(Liら、J. Org. Chem.、2008年、73巻、1963頁。)具体的には、低蛍光3−アジド−BODIPY誘導体は、CuAAC反応を受けて、増強された蛍光を有する対応するトリアゾールを得ることが示されてきた。トリアゾール生成物は、アジド−BODIPYと比較して300倍増加した発光を実現し、低い蛍光量子収率(φfl<0.03)を示したが、未反応のアジド−BODIPY化合物は不安定であり、生理学的条件下でアルキニル生体分子と反応することができず、多くの生物学的用途と不適合性なものとしている。(Wangら、Sci. China Chemistry、2012年、55巻、125頁;Chauhanら、Tetrahedron Lett.、2014年、55巻、244頁。)
(a)分子のアルキン基への本明細書に記載のような化合物のライゲーションを可能とする条件下で、化合物を、アルキン含有分子を含有する試料と共にインキュベートして、トリアゾール生成物を形成させるステップと、
(b)トリアゾール生成物から放出される蛍光シグナルを検出するステップと
を含む、方法を提供する。
(a)本明細書に記載のような化合物と、アルキン含有分子を有することが疑われる試料とを接触させるステップと、
(b)試料から放出される蛍光シグナルのレベルを検出するステップと、
(c)試料中のアルキン含有分子の存在を決定するステップと
を含み、
分子の非存在下での蛍光シグナルのレベルと比較した増強された蛍光シグナルは、アルキン含有分子の存在を示す、方法を提供する。
別の態様において、本開示は、式(IV)のシクロオクチンをベースとする蛍光発生プローブ:
G9、G10、G11、G12、G13、G14、G15、G16、G17およびG18はそれぞれの場合、独立に、水素、任意選択で置換されているC1〜6アルキル、任意選択で置換されているC1〜6アルケニル、任意選択でハロゲン、任意選択でニトロソ、任意選択で置換されているC1〜6アルキニル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBであり、
Rはそれぞれの場合、水素、ハロゲン、任意選択で置換されているアルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBから独立に選択され、
各RAは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、
各RBは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、あるいは2個のRBは、介在する窒素と一緒になって、複素環を形成し、
G9およびG10はそれぞれの場合、水素、フルオロ、クロロ、ブロモ、ヨード、ニトロソ、アルキル、アルコキシ、アリールオキシ、またはアルキニルであり、
アルキルおよびアルコキシ基は、非分岐飽和であり、1〜4個の炭素原子を有し、アリールオキシのアリール基およびアリール基は、炭素環式アリールまたは複素環式アリールのいずれかでよく、炭素環式アリール基は、置換基の炭素原子を含めて全部で6〜20個の炭素原子を有し、複素環式アリール基は、置換基の炭素原子を含めて全部で5〜20個の炭素原子を有し、カルボアルコキシ基は、カルボン酸のアルキルエステルであり、アルキル基は、上記に定義されている通りであり、各アルキル、アリール、アルコキシ、アリールオキシ、ベンゾ、およびカルボアルコキシは、独立に、非置換であるか、または1個もしくは複数の置換基で置換されていてもよく、アルキル置換基は、ハロ、ヒドロキシル、アミノ、またはアリールであり、アリール置換基は、ハロ、ヒドロキシル、アミノ、アルキル、アリール、ニトロ、またはカルボキシルであり、ハロ置換基は、フルオロまたはクロロであり、
mは、1であり、
nは、0、1、2、3、または4である
]を提供する。
(a)分子のアジド基への式(IV)の化合物のライゲーションを可能とする条件下で、化合物を、アジド含有分子を含有する試料と共にインキュベートして、トリアゾール生成物を形成させるステップと、
(b)トリアゾール生成物から放出される蛍光シグナルを検出するステップと
を含む、方法を提供する。
(a)式(IV)の化合物と、アジド含有分子を有することが疑われる試料とを接触させるステップと、
(b)試料から放出される蛍光シグナルのレベルを検出するステップと、
(c)試料中のアジド含有分子の存在を決定するステップと
を含み、
分子の非存在下での蛍光シグナルのレベルと比較した増強された蛍光シグナルは、アジド含有分子の存在を示す、方法を提供する。
(a)シアリダーゼ酵素の活性部位への請求項41に記載の化合物のライゲーションのための条件下で、化合物と、シアリダーゼ酵素を含むことが疑われる試料とを接触させ、共有結合生成物を形成させるステップと、
(b)共有結合生成物と、本明細書に記載のようなアジド含有蛍光発生プローブとを接触させて、蛍光発生トリアゾール生成物を形成させるステップと、
(c)トリアゾール生成物から放出される蛍光シグナルを測定するステップと
を含む、方法を提供する。
(a)請求項44に記載の化合物と、シアリダーゼ酵素分子を有することが疑われる試料とを接触させるステップと、
(b)試料混合物中のクマジンから放出される蛍光シグナルのレベルを測定するステップと、
(c)試料中のシアリダーゼ酵素分子の存在を決定するステップと
を含む、試料中のシアリダーゼ酵素の活性部位を検出する方法であって、
分子の非存在下での蛍光シグナルのレベルと比較した増強された蛍光シグナルは、アジド含有分子の存在を示す、方法を提供する。
あるいは炭素原子上の2個のジェミナルな水素は、基=O、=S、=NN(Rbb)2、=NNRbbC(=O)Raa、=NNRbbC(=O)ORaa、=NNRbbS(=O)2Raa、=NRbb、または=NORccで置き換えられており、
Raaはそれぞれの場合、独立に、C1〜10アルキル、C1〜10ペルハロアルキル、C2〜10アルケニル、C2〜10アルキニル、C1〜10ヘテロアルキル、C2〜10ヘテロアルケニル、C2〜10ヘテロアルキニル、C3〜10カルボシクリル、3〜14員のヘテロシクリル、C6〜14アリール、および5〜14員のヘテロアリールから選択され、あるいは2個のRaa基は接合して、3〜14員のヘテロシクリルまたは5〜14員のヘテロアリール環を形成し、各アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボシクリル、ヘテロシクリル、アリール、およびヘテロアリールは、0個、1個、2個、3個、4個、または5個のRdd基で独立に置換されており、
Rbbはそれぞれの場合、独立に、水素、−OH、−ORaa、−N(Rcc)2、−CN、−C(=O)Raa、−C(=O)N(Rcc)2、−CO2Raa、−SO2Raa、−C(=NRcc)ORaa、−C(=NRcc)N(Rcc)2、−SO2N(Rcc)2、−SO2Rcc、−SO2ORcc、−SORaa、−C(=S)N(Rcc)2、−C(=O)SRcc、−C(=S)SRcc、−P(=O)2Raa、−P(=O)(Raa)2、−P(=O)2N(Rcc)2、−P(=O)(NRcc)2、C1〜10アルキル、C1〜10ペルハロアルキル、C2〜10アルケニル、C2〜10アルキニル、C1〜10ヘテロアルキル、C2〜10ヘテロアルケニル、C2〜10ヘテロアルキニル、C3〜10カルボシクリル、3〜14員のヘテロシクリル、C6〜14アリール、および5〜14員のヘテロアリールから選択され、あるいは2個のRbb基は接合して、3〜14員のヘテロシクリルまたは5〜14員のヘテロアリール環を形成し、各アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボシクリル、ヘテロシクリル、アリール、およびヘテロアリールは、0個、1個、2個、3個、4個、または5個のRdd基で独立に置換されており、
Rccはそれぞれの場合、独立に、水素、C1〜10アルキル、C1〜10ペルハロアルキル、C2〜10アルケニル、C2〜10アルキニル、C1〜10ヘテロアルキル、C2〜10ヘテロアルケニル、C2〜10ヘテロアルキニル、C3〜10カルボシクリル、3〜14員のヘテロシクリル、C6〜14アリール、および5〜14員のヘテロアリールから選択され、あるいは2個のRcc基は接合して、3〜14員のヘテロシクリルまたは5〜14員のヘテロアリール環を形成し、各アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボシクリル、ヘテロシクリル、アリール、およびヘテロアリールは、0個、1個、2個、3個、4個、または5個のRdd基で独立に置換されており、
Rddはそれぞれの場合、独立に、ハロゲン、−CN、−NO2、−N3、−SO2H、−SO3H、−OH、−ORee、−ON(Rff)2、−N(Rff)2、−N(Rff)3 +X−、−N(ORee)Rff、−SH、−SRee、−SSRee、−C(=O)Ree、−CO2H、−CO2Ree、−OC(=O)Ree、−OCO2Ree、−C(=O)N(Rff)2、−OC(=O)N(Rff)2、−NRffC(=O)Ree、−NRffCO2Ree、−NRffC(=O)N(Rff)2、−C(=Rff)ORee、−OC(=NRff)Ree、−OC(=NRff)ORee、−C(=NRff)N(Rff)2、−OC(=NRff)N(Rff)2、−NRffC(=NRff)N(Rff)2、−NRffSO2Ree、−SO2N(Rff)2、−SO2Ree、−SO2ORee、−OSO2Ree、−S(=O)Ree、−Si(Ree)3、−OSi(Ree)3、−C(=S)N(Rff)2、−C(=O)SRee、−C(=S)SRee、−SC(=S)SRee、−P(=O)2Ree、−P(=O)(Ree)2、−OP(=O)(Ree)2、−OP(=O)(ORee)2、C1〜6アルキル、C1〜6ペルハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C1〜6ヘテロアルキル、C2〜6ヘテロアルケニル、C2〜6ヘテロアルキニル、C3〜10カルボシクリル、3〜10員のヘテロシクリル、C6〜10アリール、5〜10員のヘテロアリールから選択され、各アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボシクリル、ヘテロシクリル、アリール、およびヘテロアリールは、0個、1個、2個、3個、4個、または5個のRgg基で独立に置換されており、あるいは2個のジェミナルなRdd置換基は接合して、=Oまたは=Sを形成することができ、
Reeはそれぞれの場合、独立に、C1〜6アルキル、C1〜6ペルハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C1〜6ヘテロアルキル、C2〜6ヘテロアルケニル、C2〜6ヘテロアルキニル、C3〜10カルボシクリル、C6〜10アリール、3〜10員のヘテロシクリル、および3〜10員のヘテロアリールから選択され、各アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボシクリル、ヘテロシクリル、アリール、およびヘテロアリールは、0個、1個、2個、3個、4個、または5個のRgg基で独立に置換されており、
Rffはそれぞれの場合、独立に、水素、C1〜6アルキル、C1〜6ペルハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C1〜6ヘテロアルキル、C2〜6ヘテロアルケニル、C2〜6ヘテロアルキニル、C3〜10カルボシクリル、3〜10員のヘテロシクリル、C6〜10アリールおよび5〜10員のヘテロアリールから選択され、あるいは2個のRff基は接合して、3〜14員のヘテロシクリルまたは5〜14員のヘテロアリール環を形成し、各アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボシクリル、ヘテロシクリル、アリール、およびヘテロアリールは、0個、1個、2個、3個、4個、または5個のRgg基で独立に置換されており、
Rggはそれぞれの場合、独立に、ハロゲン、−CN、−NO2、−N3、−SO2H、−SO3H、−OH、−OC1〜6アルキル、−ON(C1〜6アルキル)2、−N(C1〜6アルキル)2、−N(C1〜6アルキル)3 +X−、−NH(C1〜6アルキル)2 +X−、−NH2(C1〜6アルキル)+X−、−NH3 +X−、−N(OC1〜6アルキル)(C1〜6アルキル)、−N(OH)(C1〜6アルキル)、−NH(OH)、−SH、−SC1〜6アルキル、−SS(C1〜6アルキル)、−C(=O)(C1〜6アルキル)、−CO2H、−CO2(C1〜6アルキル)、−OC(=O)(C1〜6アルキル)、−OCO2(C1〜6アルキル)、−C(=O)NH2、−C(=O)N(C1〜6アルキル)2、−OC(=O)NH(C1〜6アルキル)、−NHC(=O)(C1〜6アルキル)、−N(C1〜6アルキル)C(=O)(C1〜6アルキル)、−NHCO2(C1〜6アルキル)、−NHC(=O)N(C1〜6アルキル)2、−NHC(=O)NH(C1〜6アルキル)、−NHC(=O)NH2、−C(=NH)O(C1〜6アルキル)、−OC(=NH)(C1〜6アルキル)、−OC(=NH)OC1〜6アルキル、−C(=NH)N(C1〜6アルキル)2、−C(=NH)NH(C1〜6アルキル)、−C(=NH)NH2、−OC(=NH)N(C1〜6アルキル)2、−OC(NH)NH(C1〜6アルキル)、−OC(NH)NH2、−NHC(NH)N(C1〜6アルキル)2、−NHC(=NH)NH2、−NHSO2(C1〜6アルキル)、−SO2N(C1〜6アルキル)2、−SO2NH(C1〜6アルキル)、−SO2NH2、−SO2C1〜6アルキル、−SO2OC1〜6アルキル、−OSO2C1〜6アルキル、−SOC1〜6アルキル、−Si(C1〜6アルキル)3、−OSi(C1〜6アルキル)3 −C(=S)N(C1〜6アルキル)2、C(=S)NH(C1〜6アルキル)、C(=S)NH2、−C(=O)S(C1〜6アルキル)、−C(=S)SC1〜6アルキル、−SC(=S)SC1〜6アルキル、−P(=O)2(C1〜6アルキル)、−P(=O)(C1〜6アルキル)2、−OP(=O)(C1〜6アルキル)2、−OP(=O)(OC1〜6アルキル)2、C1〜6アルキル、C1〜6ペルハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C1〜6ヘテロアルキル、C2〜6ヘテロアルケニル、C2〜6ヘテロアルキニル、C3〜10カルボシクリル、C6〜10アリール、3〜10員のヘテロシクリル、5〜10員のヘテロアリールであり、あるいは2個のジェミナルなRgg置換基は接合して、=Oまたは=Sを形成することができ、式中、X−は、対イオンである。
アジド−BODIPY化合物
G1、G2、G3、G5、G6、G7およびG8はそれぞれの場合、独立に、水素、任意選択で置換されているC1〜6アルキル、任意選択で置換されているC1〜6アルケニル、任意選択で置換されているC1〜6アルキニル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBであり、
Rはそれぞれの場合、水素、ハロゲン、任意選択で置換されているアルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBから独立に選択され、
各RAは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、
各RBは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、あるいは2個のRBは、介在する窒素と一緒になって、複素環を形成し、
G4aおよびG4bはそれぞれの場合、フルオロ、アルキル、アルコキシ、アリールオキシ、またはアルキニルであり、
アルキルおよびアルコキシ基は、非分岐飽和であり、1〜4個の炭素原子を有し、アリールオキシのアリール基およびアリール基は、炭素環式アリールまたは複素環式アリールのいずれかでよく、炭素環式アリール基は、置換基の炭素原子を含めて全部で6〜20個の炭素原子を有し、複素環式アリール基は、置換基の炭素原子を含めて全部で5〜20個の炭素原子を有し、カルボアルコキシ基は、カルボン酸のアルキルエステルであり、アルキル基は、上記に定義されている通りであり、各アルキル、アリール、アルコキシ、アリールオキシ、ベンゾ、およびカルボアルコキシは、独立に、非置換であるか、または1個もしくは複数の置換基で置換されていてもよく、アルキル置換基は、ハロ、ヒドロキシル、アミノ、またはアリールであり、アリール置換基は、ハロ、ヒドロキシル、アミノ、アルキル、アリール、ニトロ、またはカルボキシルであり、ハロ置換基は、フルオロまたはクロロであり、
nは、0、1、2、3、または4である。
アルキン含有分子
トリアゾリル−BODIPY化合物
式中、
G1、G2、G3、G5、G6、G7およびG8はそれぞれの場合、独立に、水素、任意選択で置換されているC1〜6アルキル、任意選択で置換されているC1〜6アルケニル、任意選択で置換されているC1〜6アルキニル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBであり、
Rはそれぞれの場合、水素、ハロゲン、任意選択で置換されているアルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBから独立に選択され、
各RAは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、
各RBは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、あるいは2個のRBは、介在する窒素と一緒になって、複素環を形成し、
G4aおよびG4bはそれぞれの場合、フルオロ、アルキル、アルコキシ、アリールオキシ、またはアルキニルであり、
アルキルおよびアルコキシ基は、非分岐飽和であり、1〜4個の炭素原子を有し、アリールオキシのアリール基およびアリール基は、炭素環式アリールまたは複素環式アリールのいずれかでよく、炭素環式アリール基は、置換基の炭素原子を含めて全部で6〜20個の炭素原子を有し、複素環式アリール基は、置換基の炭素原子を含めて全部で5〜20個の炭素原子を有し、カルボアルコキシ基は、カルボン酸のアルキルエステルであり、アルキル基は、上記に定義されている通りであり、各アルキル、アリール、アルコキシ、アリールオキシ、ベンゾ、およびカルボアルコキシは、独立に、非置換であるか、または1個もしくは複数の置換基で置換されていてもよく、アルキル置換基は、ハロ、ヒドロキシル、アミノ、またはアリールであり、アリール置換基は、ハロ、ヒドロキシル、アミノ、アルキル、アリール、ニトロ、またはカルボキシルであり、ハロ置換基は、フルオロまたはクロロであり、
nは、0、1、2、3、または4である。
シクロオクチンをベースとする蛍光発生プローブ
シクロオクチンをベースとする蛍光発生プローブは、式(IV):
G9、G10、G11、G12、G13、G14、G15、G16、G17およびG18はそれぞれの場合、独立に、水素、任意選択で置換されているC1〜6アルキル、任意選択で置換されているC1〜6アルケニル、任意選択でハロゲン、任意選択でニトロソ、任意選択で置換されているC1〜6アルキニル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBであり、
Rはそれぞれの場合、水素、ハロゲン、任意選択で置換されているアルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBから独立に選択され、
各RAは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、
各RBは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、あるいは2個のRBは、介在する窒素と一緒になって、複素環を形成し、
G9およびG10はそれぞれの場合、水素、フルオロ、クロロ、ブロモ、ヨード、ニトロソ、アルキル、アルコキシ、アリールオキシ、またはアルキニルであり、
アルキルおよびアルコキシ基は、非分岐飽和であり、1〜4個の炭素原子を有し、アリールオキシのアリール基およびアリール基は、炭素環式アリールまたは複素環式アリールのいずれかでよく、炭素環式アリール基は、置換基の炭素原子を含めて全部で6〜20個の炭素原子を有し、複素環式アリール基は、置換基の炭素原子を含めて全部で5〜20個の炭素原子を有し、カルボアルコキシ基は、カルボン酸のアルキルエステルであり、アルキル基は、上記に定義されている通りであり、各アルキル、アリール、アルコキシ、アリールオキシ、ベンゾ、およびカルボアルコキシは、独立に、非置換であるか、または1個もしくは複数の置換基で置換されていてもよく、アルキル置換基は、ハロ、ヒドロキシル、アミノ、またはアリールであり、アリール置換基は、ハロ、ヒドロキシル、アミノ、アルキル、アリール、ニトロ、またはカルボキシルであり、ハロ置換基は、フルオロまたはクロロであり、
mは、1である。
活性をベースとする酵素プローブ
いくつかの実施形態では、本明細書に記載されている活性をベースとするプローブ(ABP)を使用して、シアリダーゼ酵素を検出および同定することができる。図26において示すように、ABPは、シアリダーゼの活性部位と反応して、共有結合を形成することができる。細胞を任意選択で溶解することができる。ABPは、アジド含有レポーター分子(例えば、本明細書に記載されているアジド含有蛍光発生プローブ)とさらに反応して、トリアゾール錯体を形成することができる。次いで、トリアゾール錯体を、検出することができる(例えば、質量分析法、蛍光、ルミネセンス、吸収分光法による)。図15.シアリダーゼの同定のための蛍光発生反応。
アジド−BODIPY化合物の合成
材料
他に示さない限り、全ての試薬は市販であり、それ以上精製することなく使用した。他に示さない限り、全ての溶媒は無水グレードであった。特に断りのない限り、全ての非水性反応は、アルゴンの僅かな陽圧下でオーブン乾燥させたガラス器具中で行った。反応を磁気的に撹拌し、シリカゲル上の薄層クロマトグラフィーによってモニターした。カラムクロマトグラフィーは、40〜63μm粒径のシリカゲル上で行った。収率は分光学的に純粋な化合物について報告する。
機器
トリアゾリル−BODIPY化合物の合成
2,6−ジエチル−4,4−ジフルオロ−8−(3−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(1)。
2,6−ジエチル−4,4−ジフルオロ−8−(2−メトキシ−5−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(2)。
2,6−ジエチル−4,4−ジフルオロ−8−(3,4−ジメトキシ−5−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(3)。
2,6−ジエチル−4,4−ジフルオロ−8−(2,3−ジメトキシ−5−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(4)。
2,6−ジエチル−4,4−ジフルオロ−8−(2,5−ジメトキシ−3−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(5)。
2,6−ジエチル−4,4−ジフルオロ−8−(2−モルホリノ−5−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(6)。
2,6−ジエチル−4,4−ジフルオロ−8−[2−(4−メチルピペラジノ)−5−ニトロフェニル]−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(7)。
2,6−ジエチル−4,4−ジフルオロ−8−(2−ピペリジノ−5−ニトロフェニル−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(8)。
4,4−ジフルオロ−8−(2−メトキシ−5−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(9)。
2,6−ジエトキシカルボニル−4,4−ジフルオロ−8−(2−メトキシ−5−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(10)。
2,6−ジシアノ−4,4−ジフルオロ−8−(2−メトキシ−5−ニトロフェニル)−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(11)。
アジド−BODIPY(Az1〜Az11)の一般合成手順および生成物特性決定。
8−(5−アミノ−2−メトキシフェニル)−2,6−ジエトキシカルボニル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Am10)。
8−(3−アジドフェニル)−2,6−ジエチル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az1)。
8−(5−アジド−2−メトキシフェニル)−2,6−ジエチル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az2)。
8−(3−アジド−4.5−ジメトキシフェニル)−2,6−ジエチル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az3)。
8−(5−アジド−2.3−ジメトキシフェニル)−2,6−ジエチル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az4)。
8−(3−アジド−2,5−ジメトキシフェニル)−2,6−ジエチル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az5)。
8−(5−アジド−2−モルホリノフェニル)−2,6−ジエチル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az6)。
8−[5−アジド−2−(4−メチルピペラジノ)フェニル]−2,6−ジエチル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az7)。
8−(5−アジド−2−ピペリジノフェニル)−2,6−ジエチル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az8)。
8−(5−アジド−2−メトキシフェニル)−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az9)。
8−(5−アジド−2−メトキシフェニル)−2,6−ジエトキシカルボニル−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az10)。
8−(5−アジド−2−メトキシフェニル)−2,6−ジシアノ−4,4−ジフルオロ−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(Az11)。
4−ペンチン−1−オールとのアジド−BODIPYの銅(I)によって触媒されるアジド−アルキン環化付加反応のための手順。
2,6−ジエチル−4,4−ジフルオロ−8−{3−[4−(3−ヒドロキシプロピル)−1H−1,2,3−トリアゾール−1−イル]−2−メトキシフェニル}−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(T2)。
4,4−ジフルオロ−8−{3−[4−(3−ヒドロキシプロピル)−1H−1,2,3−トリアゾール−1−イル]−2−メトキシフェニル}−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(T9)。
2,6−ジエトキシカルボニル−4,4−ジフルオロ−8−{3−[4−(3−ヒドロキシプロピル)−1H−1,2,3−トリアゾール−1−イル]−2−メトキシフェニル}−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(T10)。
2,6−ジシアノ−4,4−ジフルオロ−8−{3−[4−(3−ヒドロキシプロピル)−1H−1,2,3−トリアゾール−1−イル]−1,3,5,7−テトラメチル−4−ボラ−3a,4a−ジアザ−s−インダセン(T11)。
(実施例3)
生体分子の検出およびイメージング
分光学的測定
φ試料=φ標準(A標準/A試料)(F試料/F標準)(n試料/n標準)2
式中、「φ」は、量子収率であり、「A」は、励起頻度における吸光度であり、「F」は、発光曲線下積分面積であり、「n」は、使用した溶媒の屈折率である。0.1MのNaOH水溶液中のフルオレセイン(φf=0.85)、およびエタノール中のローダミン6G(φf=0.95)は、蛍光標準である。(Parker, C. A.;Rees, W. T. Analyst、1960年、85巻、587〜600頁;Kubin, R. F.;Fletcher, A. N. J. Luminescence、1982年、27巻、455〜462頁。)
マイクロタイタープレートにおけるCuAAC反応の蛍光スクリーニングの手順。
AzBOCEt(Az10)によるタンパク質標識化
細胞中の蛍光標識化の顕微鏡分析
細胞抽出物中のアルキンタグ付きシアリル糖タンパク質の検出および同定
(実施例4)
シクロオクチン官能化された蛍光プローブ101の合成:
3−アミノ−6,7,8,9−テトラヒドロベンゾシクロヘプテン−5−オン(B)。
3−ヒドロキシ−6,7,8,9−テトラヒドロベンゾシクロヘプテン−5−オン(104)。
3−ベンジルオキシ−6,7,8,9−テトラヒドロベンゾシクロヘプテン−5−オン(105)。
3−ベンジルオキシ−7,8,9,10−テトラヒドロ−5H−ベンゾシクロオクテン−6−オン(106)。
3−ベンジルオキシ−6−トリイソプロピルシリルオキシ−5,6,7,8,9,10−ヘキサヒドロベンゾシクロオクテン(107)。
3−ヒドロキシ−6−トリイソプロピルシリルオキシ−5,6,7,8,9,10−ヘキサヒドロベンゾシクロオクテン−2−カルボキサルデヒド(108)。
6,7,8,9,10,11−ヘキサヒドロ−10−トリイソプロピルシリルオキシ−シクロオクタ[g]クロメン−2(2H)−オン(109)
6,7,8,9−テトラヒドロ−11H−10−オキソ−シクロオクタ[g]クロメン−2(2H)−オン(110)
6,7,8,9−テトラヒドロ−10,11−ジデヒドロ−シクロオクタ[g]クロメン−2(2H)−オン(101)
10−ベンジル−6,7,8,9−テトラヒドロ−シクロオクタトリアゾロ[5,4−g]クロメン−2(2H)−オン(111)
N−[2−(11−オキソ−4,6,7,11−テトラヒドロクロメノ[7’,6’:3,4]シクロオクタ[1,2−d][1,2,3]トリアゾール−3(5H)−イル)]アセトアミド−2−デオキシ−α,β−D−マンノピラノース(112)
(実施例5)
モデル基質を使用したシクロオクチンが縮合した蛍光発生プローブの反応スコープおよび反応速度の測定
(実施例6)
シクロオクチン縮合した蛍光発生プローブ101を使用した染色された試料の生細胞イメージング:
蛍光分光法による時間経過測定。
生細胞における蛍光標識化のタイムラプス顕微鏡分析。
生細胞における蛍光標識化によるシアリルコンジュゲート輸送の顕微鏡分析。
実験7:二重標識化実験
細胞におけるデュアル蛍光標識化の顕微鏡分析。
実験8:3−メルカプトプロピオン酸の存在下での化合物(101)および化合物(111)の安定性
(実施例9)
CoumFSA(601)の合成。
(実施例10)
DFSA(501)の合成。
参照文献
Claims (46)
- 式(I)の化合物:
[式中、
G1、G2、G3、G5、G6、G7およびG8はそれぞれの場合、独立に、水素、任意選択で置換されているC1〜6アルキル、任意選択で置換されているC1〜6アルケニル、任意選択で置換されているC1〜6アルキニル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBであり、
Rはそれぞれの場合、水素、ハロゲン、任意選択で置換されているアルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBから独立に選択され、
各RAは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、
各RBは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、あるいは2個のRBは、介在する窒素と一緒になって、複素環を形成し、
G4aおよびG4bはそれぞれの場合、フルオロ、アルキル、アルコキシ、アリールオキシ、またはアルキニルであり、
アルキルおよびアルコキシ基は、非分岐飽和であり、1〜4個の炭素原子を有し、アリール基およびアリールオキシのアリール基は、炭素環式アリールまたは複素環式アリールのいずれかでよく、炭素環式アリール基は、置換基の炭素原子を含めて全部で6〜20個の炭素原子を有し、複素環式アリール基は、置換基の炭素原子を含めて全部で5〜20個の炭素原子を有し、カルボアルコキシ基は、カルボン酸のアルキルエステルであり、アルキル基は、上記に定義されている通りであり、各アルキル、アリール、アルコキシ、アリールオキシ、ベンゾ、およびカルボアルコキシは、独立に、非置換であるか、または1個もしくは複数の置換基で置換されていてもよく、アルキル置換基は、ハロ、ヒドロキシル、アミノ、またはアリールであり、アリール置換基は、ハロ、ヒドロキシル、アミノ、アルキル、アリール、ニトロ、またはカルボキシルであり、ハロ置換基は、フルオロまたはクロロであり、
nは、0、1、2、3、または4である]。 - G1およびG3が、メチルである、請求項1に記載の化合物。
- G5およびG7が、メチルである、請求項1に記載の化合物。
- 式(II)のもの、
- 表1から選択される式によって記載される、請求項4に記載の化合物。
-
- アルキン含有分子をイメージングする方法であって、
(a)前記分子のアルキン基への請求項1に記載の化合物のライゲーションのための条件下で、前記化合物と、前記アルキン含有分子を含有する試料とを接触させ、トリアゾール生成物を形成させるステップと、
(b)前記トリアゾール生成物から放出される蛍光シグナルを測定するステップと
を含む、方法。 - 前記接触ステップが、金属触媒の存在下で行われる、請求項7に記載の方法。
- 前記金属触媒が、銅(I)である、請求項8に記載の方法。
- 前記化合物が、前記アルキン基に共有結合的に連結している、請求項7に記載の方法。
- 前記試料が、細胞を含有し、前記アルキン含有分子が、細胞表面上または前記細胞内に位置している、請求項7に記載の方法。
- 前記化合物が、表1から選択される式によって記載される、請求項7に記載の方法。
- 前記化合物が、請求項6に記載の化合物から選択される、請求項7に記載の方法。
- 前記アルキン含有分子が、生体分子である、請求項7から11のいずれか一項に記載の方法。
- 前記生体分子が、DNA、RNA、タンパク質またはグリカンである、請求項14に記載の方法。
- 前記生体分子が、細胞の表面上または近くに位置している、請求項14に記載の方法。
- 前記生体分子が、細胞内生体分子である、請求項14に記載の方法。
- 試料中のアルキン含有分子を検出する方法であって、
(a)請求項1に記載の化合物と、アルキン含有分子を有することが疑われる試料とを接触させるステップと、
(b)試料混合物から放出される蛍光シグナルのレベルを測定するステップと、
(c)前記試料中の前記アルキン含有分子の存在を決定するステップと
を含み、前記分子の非存在下での蛍光シグナルのレベルと比較した増強された蛍光シグナルは、前記アルキン含有分子の存在を示す、方法。 - 前記接触ステップが、金属触媒の存在下で行われる、請求項18に記載の方法。
- 前記金属触媒が、銅(I)である、請求項19に記載の方法。
- 前記試料が、細胞を含有し、前記アルキン含有分子が、細胞の表面上もしくは近く、または細胞内に位置している、請求項18から20のいずれか一項に記載の方法。
- 前記化合物が、表1から選択される式によって記載される、請求項18に記載の方法。
- 前記化合物が、請求項6に記載の化合物から選択される、請求項18に記載の方法。
- 前記アルキン含有分子が、生体分子である、請求項18に記載の方法。
- 前記生体分子が、DNA、RNA、タンパク質またはグリカンである、請求項24に記載の方法。
- 前記生体分子が、細胞の表面上または近くに位置している、請求項24に記載の方法。
- 前記生体分子が、細胞内生体分子である、請求項24に記載の方法。
- 細胞におけるデュアル蛍光イメージングのための前記化合物の使用を含む、請求項7または18に記載の方法。
- 式(IV)の化合物:
[式中、
G9、G10、G11、G12、G13、G14、G15、G16、G17およびG18はそれぞれの場合、独立に、水素、任意選択で置換されているC1〜6アルキル、任意選択で置換されているC1〜6アルケニル、任意選択でハロゲン、任意選択でニトロソ、任意選択で置換されているC1〜6アルキニル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBであり、
Rはそれぞれの場合、水素、ハロゲン、任意選択で置換されているアルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、任意選択で置換されているアリール、任意選択で置換されているアシル、−ORA、−CH2ORA、−OC(O)RA、−SRA、−N(RB)2、−N(RA)C(O)RA、−C(O)N(RB)2、−CN、−NO2、−C(O)RA、−C(O)ORA、−S(O)RA、−SO2RA、−SO3RA、−SO2N(RB)2、および−NHSO2RBから独立に選択され、
各RAは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、
各RBは、水素、任意選択で置換されているC1〜C6アルキル、任意選択で置換されているアルケニル、任意選択で置換されているアルキニル、任意選択で置換されているヘテロシクリル、および任意選択で置換されているアリールから独立に選択され、あるいは2個のRBは、介在する窒素と一緒になって、複素環を形成し、
G9およびG10はそれぞれの場合、水素、フルオロ、クロロ、ブロモ、ヨード、ニトロソ、アルキル、アルコキシ、アリールオキシ、またはアルキニルであり、
アルキルおよびアルコキシ基は、非分岐飽和であり、1〜4個の炭素原子を有し、アリールオキシのアリール基およびアリール基は、炭素環式アリールまたは複素環式アリールのいずれかでよく、炭素環式アリール基は、置換基の炭素原子を含めて全部で6〜20個の炭素原子を有し、複素環式アリール基は、置換基の炭素原子を含めて全部で5〜20個の炭素原子を有し、カルボアルコキシ基は、カルボン酸のアルキルエステルであり、アルキル基は、上記に定義されている通りであり、各アルキル、アリール、アルコキシ、アリールオキシ、ベンゾ、およびカルボアルコキシは、独立に、非置換であるか、または1個もしくは複数の置換基で置換されていてもよく、アルキル置換基は、ハロ、ヒドロキシル、アミノ、またはアリールであり、アリール置換基は、ハロ、ヒドロキシル、アミノ、アルキル、アリール、ニトロ、またはカルボキシルであり、ハロ置換基は、フルオロまたはクロロであり、
mは、1である]。 - G9およびG10が、水素である、請求項29に記載の化合物。
- G9およびG10が、ハロゲンである、請求項29に記載の化合物。
- G9およびG10が、フッ素である、請求項31に記載の化合物。
- 化合物101
- アジド含有分子をイメージングする方法であって、
(a)前記分子のアジド基への請求項29に記載の化合物のライゲーションのための条件下で、前記化合物と、前記アジド含有分子を含有する試料とを接触させ、トリアゾール生成物を形成させるステップと、
(b)前記トリアゾール生成物から放出される蛍光シグナルを測定するステップと
を含む、方法。 - 試料中のアジド含有分子を検出する方法であって、
(a)請求項29に記載の化合物と、アジド含有分子を有することが疑われる試料とを接触させるステップと、
(b)試料混合物から放出される蛍光シグナルのレベルを測定するステップと、
(c)前記試料中の前記アジド含有分子の存在を決定するステップと
を含み、前記分子の非存在下での蛍光シグナルのレベルと比較した増強された蛍光シグナルは、前記アジド含有分子の存在を示す、方法。 - (a)1−ベンゾスベロンの8位における位置選択的ニトロ化;
(b)1−ベンゾスベロンの8位におけるニトロ基の還元;
(c)還元されたニトロ基の酸条件下でのジアゾ化およびヒドロキシル化による、アルコールの形成;
(d)ベンジルエーテルとしての前記アルコール上のヒドロキシル基の保護;
(e)BF3・OEt2の存在下でのTMS−ジアゾメタンによる処理による環状ケトン上の環の拡張;
(f)NaBH4によるシクロオクタノン上のカルボニル基の還元;
(g)前記還元されたカルボニル基のシリル化による、シリルエーテルの形成;
(h)水素化による前記アルコール上のベンジル保護基の除去による、フェノールの形成;
(i)Et3NおよびMgCl2の存在下での過剰なパラホルムアルデヒドによる前記フェノールの処理による、サリチルアルデヒドの形成;
(j)新たに調製したケテニリデントリフェニルホスホランによる前記サリチルアルデヒドの処理;
(k)前記ケテニリデントリフェニルホスホラン処理したサリチルアルデヒドの脱シリル化および酸化による、ケトンの形成、
(l)エノールトリフレートへの前記ケトン中の前記カルボニル基の変換;
(m)強塩基NaHMDSによる前記エノールトリフレートの処理による脱離反応、それによる最終生成物101の生成
を含む、請求項33に記載の化合物を生成する方法。 - 式(V)の化合物:
- Lが、ハロゲンである、請求項37に記載の化合物。
- Lが、フッ素である、請求項38に記載の化合物。
- クマリンである、請求項37に記載の化合物。
- 式(VI)の化合物:
- Lが、ハロゲンである、請求項41に記載の化合物。
- Lが、化合物501である、請求項41に記載の化合物。
- 化合物601である、請求項41に記載の化合物。
- シアリダーゼ酵素の活性部位をイメージングする方法であって、
(a)前記シアリダーゼ酵素の前記活性部位への請求項41に記載の化合物のライゲーションのための条件下で、前記化合物と、前記シアリダーゼ酵素を含むことが疑われる試料とを接触させ、共有結合生成物を形成させるステップと、
(b)前記共有結合生成物と、本明細書に記載のようなアジド含有蛍光発生プローブとを接触させて、蛍光発生トリアゾール生成物を形成させるステップと、
(c)前記トリアゾール生成物から放出される蛍光シグナルを測定するステップと
を含む、方法。 - 試料中のシアリダーゼ酵素の活性部位を検出する方法であって、
(a)請求項41に記載の化合物と、シアリダーゼ酵素分子を有することが疑われる試料とを接触させるステップと、
(b)試料混合物中のクマジンから放出される蛍光シグナルのレベルを測定するステップと、
(c)前記試料中の前記シアリダーゼ酵素分子の存在を決定するステップと
を含み、
前記分子の非存在下での蛍光シグナルのレベルと比較した増強された蛍光シグナルは、アジド含有分子の存在を示す、方法。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020139782A (ja) * | 2019-02-27 | 2020-09-03 | 公立大学法人福井県立大学 | 生体高分子を認識するハイブリッド型蛍光プローブ |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
EP2318832B1 (en) | 2008-07-15 | 2013-10-09 | Academia Sinica | Glycan arrays on ptfe-like aluminum coated glass slides and related methods |
US11377485B2 (en) | 2009-12-02 | 2022-07-05 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
US10338069B2 (en) | 2010-04-12 | 2019-07-02 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
US9914956B2 (en) * | 2012-08-18 | 2018-03-13 | Academia Sinica | Cell-permeable probes for identification and imaging of sialidases |
EP3013365B1 (en) | 2013-06-26 | 2019-06-05 | Academia Sinica | Rm2 antigens and use thereof |
WO2014210564A1 (en) | 2013-06-27 | 2014-12-31 | Academia Sinica | Glycan conjugates and use thereof |
US9782476B2 (en) | 2013-09-06 | 2017-10-10 | Academia Sinica | Human iNKT cell activation using glycolipids with altered glycosyl groups |
US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
JP2017507118A (ja) | 2014-01-16 | 2017-03-16 | アカデミア シニカAcademia Sinica | がんの処置および検出のための組成物および方法 |
TWI687428B (zh) | 2014-03-27 | 2020-03-11 | 中央研究院 | 反應性標記化合物及其用途 |
KR102512592B1 (ko) | 2014-05-27 | 2023-03-21 | 아카데미아 시니카 | 항-her2 글리코항체 및 이의 용도 |
CA2950415A1 (en) | 2014-05-27 | 2015-12-03 | Academia Sinica | Anti-cd20 glycoantibodies and uses thereof |
US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
EP3149045B1 (en) | 2014-05-27 | 2023-01-18 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
KR102494193B1 (ko) | 2014-05-28 | 2023-01-31 | 아카데미아 시니카 | 항-tnf-알파 글리코항체 및 이의 용도 |
KR102422375B1 (ko) | 2014-09-08 | 2022-07-18 | 아카데미아 시니카 | 당지질을 사용한 인간 iNKT 세포 활성화 |
US9975965B2 (en) | 2015-01-16 | 2018-05-22 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
US10495645B2 (en) | 2015-01-16 | 2019-12-03 | Academia Sinica | Cancer markers and methods of use thereof |
EP3248005B1 (en) | 2015-01-24 | 2020-12-09 | Academia Sinica | Novel glycan conjugates and methods of use thereof |
JP2019515876A (ja) | 2016-03-08 | 2019-06-13 | アカデミア シニカAcademia Sinica | N−グリカンおよびそのアレイのモジュール合成のための方法 |
WO2017196954A1 (en) * | 2016-05-10 | 2017-11-16 | Sony Corporation | Ultra bright polymeric dyes with peptide backbones |
CN109963868B (zh) | 2016-08-22 | 2023-11-14 | 醣基生医股份有限公司 | 抗体、结合片段及使用方法 |
CN107973787B (zh) * | 2017-11-29 | 2021-02-02 | 山西大学 | 一种香豆素衍生物dmac及其制备方法和应用 |
EP3746457A1 (en) | 2018-01-29 | 2020-12-09 | Stichting Katholieke Universiteit | New potent sialyltransferase inhibitors |
CN111349109B (zh) * | 2020-04-02 | 2022-09-16 | 三峡大学 | 一种七元氟硼二吡咯荧光染料的合成方法 |
CN113004311B (zh) * | 2021-02-05 | 2022-07-19 | 嘉兴学院 | 一种氟硼二吡咯类荧光探针、其制备方法及在金离子检测中的应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20140051109A1 (en) * | 2011-03-01 | 2014-02-20 | Agency For Science, Technology And Research | Novel compounds with photoluminescence properties and applications thereof |
Family Cites Families (347)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US3896111A (en) | 1973-02-20 | 1975-07-22 | Research Corp | Ansa macrolides |
US4151042A (en) | 1977-03-31 | 1979-04-24 | Takeda Chemical Industries, Ltd. | Method for producing maytansinol and its derivatives |
US4137230A (en) | 1977-11-14 | 1979-01-30 | Takeda Chemical Industries, Ltd. | Method for the production of maytansinoids |
USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
US4265814A (en) | 1978-03-24 | 1981-05-05 | Takeda Chemical Industries | Matansinol 3-n-hexadecanoate |
US4307016A (en) | 1978-03-24 | 1981-12-22 | Takeda Chemical Industries, Ltd. | Demethyl maytansinoids |
JPS5562090A (en) | 1978-10-27 | 1980-05-10 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
US4256746A (en) | 1978-11-14 | 1981-03-17 | Takeda Chemical Industries | Dechloromaytansinoids, their pharmaceutical compositions and method of use |
JPS5566585A (en) | 1978-11-14 | 1980-05-20 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS55164687A (en) | 1979-06-11 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS55102583A (en) | 1979-01-31 | 1980-08-05 | Takeda Chem Ind Ltd | 20-acyloxy-20-demethylmaytansinoid compound |
JPS55162791A (en) | 1979-06-05 | 1980-12-18 | Takeda Chem Ind Ltd | Antibiotic c-15003pnd and its preparation |
JPS55164685A (en) | 1979-06-08 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
JPS55164686A (en) | 1979-06-11 | 1980-12-22 | Takeda Chem Ind Ltd | Novel maytansinoid compound and its preparation |
US4309428A (en) | 1979-07-30 | 1982-01-05 | Takeda Chemical Industries, Ltd. | Maytansinoids |
JPS5645483A (en) | 1979-09-19 | 1981-04-25 | Takeda Chem Ind Ltd | C-15003phm and its preparation |
EP0028683A1 (en) | 1979-09-21 | 1981-05-20 | Takeda Chemical Industries, Ltd. | Antibiotic C-15003 PHO and production thereof |
JPS5645485A (en) | 1979-09-21 | 1981-04-25 | Takeda Chem Ind Ltd | Production of c-15003pnd |
US4270537A (en) | 1979-11-19 | 1981-06-02 | Romaine Richard A | Automatic hypodermic syringe |
US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
WO1982001188A1 (en) | 1980-10-08 | 1982-04-15 | Takeda Chemical Industries Ltd | 4,5-deoxymaytansinoide compounds and process for preparing same |
US4450254A (en) | 1980-11-03 | 1984-05-22 | Standard Oil Company | Impact improvement of high nitrile resins |
US4419446A (en) | 1980-12-31 | 1983-12-06 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant DNA process utilizing a papilloma virus DNA as a vector |
US4315929A (en) | 1981-01-27 | 1982-02-16 | The United States Of America As Represented By The Secretary Of Agriculture | Method of controlling the European corn borer with trewiasine |
US4313946A (en) | 1981-01-27 | 1982-02-02 | The United States Of America As Represented By The Secretary Of Agriculture | Chemotherapeutically active maytansinoids from Trewia nudiflora |
JPS57192389A (en) | 1981-05-20 | 1982-11-26 | Takeda Chem Ind Ltd | Novel maytansinoid |
US4596792A (en) | 1981-09-04 | 1986-06-24 | The Regents Of The University Of California | Safe vaccine for hepatitis containing polymerized serum albumin |
US4741900A (en) | 1982-11-16 | 1988-05-03 | Cytogen Corporation | Antibody-metal ion complexes |
US4601978A (en) | 1982-11-24 | 1986-07-22 | The Regents Of The University Of California | Mammalian metallothionein promoter system |
US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
US4599231A (en) | 1984-03-09 | 1986-07-08 | Scripps Clinic And Research Foundation | Synthetic hepatitis B virus vaccine including both T cell and B cell determinants |
US4599230A (en) | 1984-03-09 | 1986-07-08 | Scripps Clinic And Research Foundation | Synthetic hepatitis B virus vaccine including both T cell and B cell determinants |
US4965199A (en) | 1984-04-20 | 1990-10-23 | Genentech, Inc. | Preparation of functional human factor VIII in mammalian cells using methotrexate based selection |
US4970198A (en) | 1985-10-17 | 1990-11-13 | American Cyanamid Company | Antitumor antibiotics (LL-E33288 complex) |
US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
US4601903A (en) | 1985-05-01 | 1986-07-22 | The United States Of America As Represented By The Department Of Health And Human Services | Vaccine against Neisseria meningitidis Group B serotype 2 invasive disease |
GB8516415D0 (en) | 1985-06-28 | 1985-07-31 | Celltech Ltd | Culture of animal cells |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
US5567610A (en) | 1986-09-04 | 1996-10-22 | Bioinvent International Ab | Method of producing human monoclonal antibodies and kit therefor |
US6024983A (en) | 1986-10-24 | 2000-02-15 | Southern Research Institute | Composition for delivering bioactive agents for immune response and its preparation |
US5075109A (en) | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
CA1283827C (en) | 1986-12-18 | 1991-05-07 | Giorgio Cirelli | Appliance for injection of liquid formulations |
IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
US5079233A (en) | 1987-01-30 | 1992-01-07 | American Cyanamid Company | N-acyl derivatives of the LL-E33288 antitumor antibiotics, composition and methods for using the same |
GB8704027D0 (en) | 1987-02-20 | 1987-03-25 | Owen Mumford Ltd | Syringe needle combination |
WO1988007089A1 (en) | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
US4849222A (en) | 1987-03-24 | 1989-07-18 | The Procter & Gamble Company | Mixtures for treating hypercholesterolemia |
US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
US4940460A (en) | 1987-06-19 | 1990-07-10 | Bioject, Inc. | Patient-fillable and non-invasive hypodermic injection device assembly |
US4975278A (en) | 1988-02-26 | 1990-12-04 | Bristol-Myers Company | Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells |
US5004697A (en) | 1987-08-17 | 1991-04-02 | Univ. Of Ca | Cationized antibodies for delivery through the blood-brain barrier |
US5606040A (en) | 1987-10-30 | 1997-02-25 | American Cyanamid Company | Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group |
US5770701A (en) | 1987-10-30 | 1998-06-23 | American Cyanamid Company | Process for preparing targeted forms of methyltrithio antitumor agents |
US5053394A (en) | 1988-09-21 | 1991-10-01 | American Cyanamid Company | Targeted forms of methyltrithio antitumor agents |
JP2670680B2 (ja) | 1988-02-24 | 1997-10-29 | 株式会社ビーエムジー | 生理活性物質含有ポリ乳酸系微小球およびその製造法 |
US5339163A (en) | 1988-03-16 | 1994-08-16 | Canon Kabushiki Kaisha | Automatic exposure control device using plural image plane detection areas |
JPH01287029A (ja) | 1988-05-13 | 1989-11-17 | Mect Corp | 新規抗ウィルス剤 |
AU632065B2 (en) | 1988-09-23 | 1992-12-17 | Novartis Vaccines And Diagnostics, Inc. | Cell culture medium for enhanced cell growth, culture longevity and product expression |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
FR2638359A1 (fr) | 1988-11-03 | 1990-05-04 | Tino Dalto | Guide de seringue avec reglage de la profondeur de penetration de l'aiguille dans la peau |
US5175384A (en) | 1988-12-05 | 1992-12-29 | Genpharm International | Transgenic mice depleted in mature t-cells and methods for making transgenic mice |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
EP0739904A1 (en) | 1989-06-29 | 1996-10-30 | Medarex, Inc. | Bispecific reagents for aids therapy |
US5690938A (en) | 1989-07-07 | 1997-11-25 | Oravax, Inc. | Oral immunization with multiple particulate antigen delivery system |
US5518725A (en) | 1989-09-25 | 1996-05-21 | University Of Utah Research Foundation | Vaccine compositions and method for induction of mucosal immune response via systemic vaccination |
US5208020A (en) | 1989-10-25 | 1993-05-04 | Immunogen Inc. | Cytotoxic agents comprising maytansinoids and their therapeutic use |
CA2026147C (en) | 1989-10-25 | 2006-02-07 | Ravi J. Chari | Cytotoxic agents comprising maytansinoids and their therapeutic use |
US5238843A (en) | 1989-10-27 | 1993-08-24 | Genencor International, Inc. | Method for cleaning a surface on which is bound a glycoside-containing substance |
US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
DE69133566T2 (de) | 1990-01-12 | 2007-12-06 | Amgen Fremont Inc. | Bildung von xenogenen Antikörpern |
US5061620A (en) | 1990-03-30 | 1991-10-29 | Systemix, Inc. | Human hematopoietic stem cell |
US5112596A (en) | 1990-04-23 | 1992-05-12 | Alkermes, Inc. | Method for increasing blood-brain barrier permeability by administering a bradykinin agonist of blood-brain barrier permeability |
US5268164A (en) | 1990-04-23 | 1993-12-07 | Alkermes, Inc. | Increasing blood-brain barrier permeability with permeabilizer peptides |
CZ288492B6 (en) | 1990-04-24 | 2001-06-13 | Biota Scient Management | Derivatives of alpha-D-neuraminic acid, process of their preparation, their use and pharmaceutical preparations based thereon |
JPH05506233A (ja) | 1990-04-24 | 1993-09-16 | フラスタット・ピーティーワイ・リミテッド | 赤血球の表面に結合した抗原を含むワクチン |
US5229275A (en) | 1990-04-26 | 1993-07-20 | Akzo N.V. | In-vitro method for producing antigen-specific human monoclonal antibodies |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
WO1992000373A1 (en) | 1990-06-29 | 1992-01-09 | Biosource Genetics Corporation | Melanin production by transformed microorganisms |
US5190521A (en) | 1990-08-22 | 1993-03-02 | Tecnol Medical Products, Inc. | Apparatus and method for raising a skin wheal and anesthetizing skin |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5714374A (en) | 1990-09-12 | 1998-02-03 | Rutgers University | Chimeric rhinoviruses |
US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
WO1992006691A1 (en) | 1990-10-19 | 1992-04-30 | Biota Scientific Management Pty. Ltd. | Anti-viral compounds that bind the active site of influenza neuramidase and display in vivo activity against orthomyxovirus and paramyxovirus |
US5264365A (en) | 1990-11-09 | 1993-11-23 | Board Of Regents, The University Of Texas System | Protease-deficient bacterial strains for production of proteolytically sensitive polypeptides |
US5508192A (en) | 1990-11-09 | 1996-04-16 | Board Of Regents, The University Of Texas System | Bacterial host strains for producing proteolytically sensitive polypeptides |
CA2405246A1 (en) | 1990-12-03 | 1992-06-11 | Genentech, Inc. | Enrichment method for variant proteins with alterred binding properties |
US5527288A (en) | 1990-12-13 | 1996-06-18 | Elan Medical Technologies Limited | Intradermal drug delivery device and method for intradermal delivery of drugs |
US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
WO1992019971A1 (en) | 1991-04-30 | 1992-11-12 | Alkermes, Inc. | Cationized antibodies against intracellular proteins |
CA2103059C (en) | 1991-06-14 | 2005-03-22 | Paul J. Carter | Method for making humanized antibodies |
GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
GB9118204D0 (en) | 1991-08-23 | 1991-10-09 | Weston Terence E | Needle-less injector |
SE9102652D0 (sv) | 1991-09-13 | 1991-09-13 | Kabi Pharmacia Ab | Injection needle arrangement |
CA2116774C (en) | 1991-09-19 | 2003-11-11 | Paul J. Carter | Expression in e. coli antibody fragments having at least a cysteine present as a free thiol. use for the production of bifunctional f(ab') 2 antibodies |
WO1993006213A1 (en) | 1991-09-23 | 1993-04-01 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
US5362852A (en) | 1991-09-27 | 1994-11-08 | Pfizer Inc. | Modified peptide derivatives conjugated at 2-hydroxyethylamine moieties |
US5587458A (en) | 1991-10-07 | 1996-12-24 | Aronex Pharmaceuticals, Inc. | Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof |
US5288502A (en) | 1991-10-16 | 1994-02-22 | The University Of Texas System | Preparation and uses of multi-phase microspheres |
WO1993008829A1 (en) | 1991-11-04 | 1993-05-13 | The Regents Of The University Of California | Compositions that mediate killing of hiv-infected cells |
ES2137981T3 (es) | 1991-11-19 | 2000-01-01 | Univ Virginia | Tratamiento combinado por agentes antimediaticos y antiviricos de resfriados comunes. |
JPH0826057B2 (ja) | 1992-01-16 | 1996-03-13 | 株式会社ディ・ディ・エス研究所 | シアル酸オリゴ糖誘導体及び微粒子キャリヤー |
US5667988A (en) | 1992-01-27 | 1997-09-16 | The Scripps Research Institute | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
CA2129663C (en) | 1992-02-06 | 2005-07-05 | James S. Huston | Biosynthetic binding protein for cancer marker |
US5328483A (en) | 1992-02-27 | 1994-07-12 | Jacoby Richard M | Intradermal injection device with medication and needle guard |
US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
US5326856A (en) | 1992-04-09 | 1994-07-05 | Cytogen Corporation | Bifunctional isothiocyanate derived thiocarbonyls as ligands for metal binding |
ZA932522B (en) | 1992-04-10 | 1993-12-20 | Res Dev Foundation | Immunotoxins directed against c-erbB-2(HER/neu) related surface antigens |
JP2904647B2 (ja) | 1992-06-12 | 1999-06-14 | 株式会社蛋白工学研究所 | 5−ブロム−4−クロロインド−3−イル−2−シアル酸の製造方法 |
DE69334095T2 (de) | 1992-07-17 | 2007-04-12 | Dana-Farber Cancer Institute, Boston | Verfahren zur intrazellulären Bindung von zielgerichteten Molekülen |
US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
EP0652775B1 (en) | 1992-07-27 | 2000-04-19 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by the SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Targeting of liposomes to the blood-brain barrier |
ATE149570T1 (de) | 1992-08-17 | 1997-03-15 | Genentech Inc | Bispezifische immunoadhesine |
US5569189A (en) | 1992-09-28 | 1996-10-29 | Equidyne Systems, Inc. | hypodermic jet injector |
EP0666268B1 (en) | 1992-10-22 | 2000-04-19 | Kirin Beer Kabushiki Kaisha | Novel sphingoglycolipid and use thereof |
US5807722A (en) | 1992-10-30 | 1998-09-15 | Bioengineering Resources, Inc. | Biological production of acetic acid from waste gases with Clostridium ljungdahlii |
US5334144A (en) | 1992-10-30 | 1994-08-02 | Becton, Dickinson And Company | Single use disposable needleless injector |
NZ258392A (en) | 1992-11-13 | 1997-09-22 | Idec Pharma Corp | Chimeric and radiolabelled antibodies to the b lymphocyte cellsurface antigen bp35 (cd-20) and their use in the treatment of b cell lymphona |
US5736137A (en) | 1992-11-13 | 1998-04-07 | Idec Pharmaceuticals Corporation | Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma |
US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
US5374541A (en) | 1993-05-04 | 1994-12-20 | The Scripps Research Institute | Combined use of β-galactosidase and sialyltransferase coupled with in situ regeneration of CMP-sialic acid for one pot synthesis of oligosaccharides |
US20020037517A1 (en) | 1993-05-28 | 2002-03-28 | Hutchens T. William | Methods for sequencing biopolymers |
AU691811B2 (en) | 1993-06-16 | 1998-05-28 | Celltech Therapeutics Limited | Antibodies |
CA2172509C (en) | 1993-10-22 | 2010-08-24 | Jeffrey L. Cleland | Methods and compositions for microencapsulation of antigens for use as vaccines |
US5369017A (en) | 1994-02-04 | 1994-11-29 | The Scripps Research Institute | Process for solid phase glycopeptide synthesis |
JPH09509664A (ja) | 1994-02-25 | 1997-09-30 | イー・アイ・デユポン・ドウ・ヌムール・アンド・カンパニー | 4−n−置換シアル酸およびそれらのシアロシド類 |
WO1995024176A1 (en) | 1994-03-07 | 1995-09-14 | Bioject, Inc. | Ampule filling device |
US5466220A (en) | 1994-03-08 | 1995-11-14 | Bioject, Inc. | Drug vial mixing and transfer device |
US5773001A (en) | 1994-06-03 | 1998-06-30 | American Cyanamid Company | Conjugates of methyltrithio antitumor agents and intermediates for their synthesis |
US5622701A (en) | 1994-06-14 | 1997-04-22 | Protein Design Labs, Inc. | Cross-reacting monoclonal antibodies specific for E- and P-selectin |
ATE306930T1 (de) | 1994-08-12 | 2005-11-15 | Immunomedics Inc | Für b-zell-lymphom und leukämiezellen spezifische immunkonjugate und humane antikörper |
US5639635A (en) | 1994-11-03 | 1997-06-17 | Genentech, Inc. | Process for bacterial production of polypeptides |
EP1241264A1 (en) | 1994-12-02 | 2002-09-18 | Chiron Corporation | Monoclonal antibodies to colon cancer antigen |
US5663149A (en) | 1994-12-13 | 1997-09-02 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides |
US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
US5840523A (en) | 1995-03-01 | 1998-11-24 | Genetech, Inc. | Methods and compositions for secretion of heterologous polypeptides |
US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
US6673533B1 (en) | 1995-03-10 | 2004-01-06 | Meso Scale Technologies, Llc. | Multi-array multi-specific electrochemiluminescence testing |
US5641870A (en) | 1995-04-20 | 1997-06-24 | Genentech, Inc. | Low pH hydrophobic interaction chromatography for antibody purification |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
AU707444B2 (en) | 1995-04-25 | 1999-07-08 | Irori | Remotely programmable matrices with memories and uses thereof |
KR20050085971A (ko) | 1995-04-27 | 2005-08-29 | 아브게닉스, 인크. | 면역화된 제노마우스 유래의 인간 항체 |
AU2466895A (en) | 1995-04-28 | 1996-11-18 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US5730723A (en) | 1995-10-10 | 1998-03-24 | Visionary Medical Products Corporation, Inc. | Gas pressured needle-less injection device and method |
US6265150B1 (en) | 1995-06-07 | 2001-07-24 | Becton Dickinson & Company | Phage antibodies |
US5837234A (en) | 1995-06-07 | 1998-11-17 | Cytotherapeutics, Inc. | Bioartificial organ containing cells encapsulated in a permselective polyether suflfone membrane |
US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
US5712374A (en) | 1995-06-07 | 1998-01-27 | American Cyanamid Company | Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates |
EP0840796A2 (en) | 1995-07-26 | 1998-05-13 | Maxim Pharmaceuticals | Mucosal delivery of polynucleotides |
DE19544393A1 (de) | 1995-11-15 | 1997-05-22 | Hoechst Schering Agrevo Gmbh | Synergistische herbizide Mischungen |
US5893397A (en) | 1996-01-12 | 1999-04-13 | Bioject Inc. | Medication vial/syringe liquid-transfer apparatus |
AU2660397A (en) | 1996-04-05 | 1997-10-29 | Board Of Regents, The University Of Texas System | Methods for producing soluble, biologically-active disulfide bond-containing eukaryotic proteins in bacterial cells |
GB9607549D0 (en) | 1996-04-11 | 1996-06-12 | Weston Medical Ltd | Spring-powered dispensing device |
US5922845A (en) | 1996-07-11 | 1999-07-13 | Medarex, Inc. | Therapeutic multispecific compounds comprised of anti-Fcα receptor antibodies |
US6340702B1 (en) | 1996-07-22 | 2002-01-22 | Sankyo Company, Limited | Neuraminic acid derivatives, their preparation and their medical use |
US6506564B1 (en) | 1996-07-29 | 2003-01-14 | Nanosphere, Inc. | Nanoparticles having oligonucleotides attached thereto and uses therefor |
JP3691075B2 (ja) | 1996-11-14 | 2005-08-31 | バイオタ、サイアンティフィック、マネージメント、プロプライエタリ、リミテッド | 新規化合物およびその使用方法 |
EP2314625B1 (en) | 1996-12-03 | 2014-05-07 | Amgen Fremont Inc. | Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom |
TW555562B (en) | 1996-12-27 | 2003-10-01 | Kirin Brewery | Method for activation of human antigen-presenting cells, activated human antigen-presenting cells and use thereof |
ATE332918T1 (de) | 1997-04-18 | 2006-08-15 | Novartis Pharma Gmbh | Neoglycoproteine |
US5993412A (en) | 1997-05-19 | 1999-11-30 | Bioject, Inc. | Injection apparatus |
US6083715A (en) | 1997-06-09 | 2000-07-04 | Board Of Regents, The University Of Texas System | Methods for producing heterologous disulfide bond-containing polypeptides in bacterial cells |
JPH1135593A (ja) | 1997-07-18 | 1999-02-09 | Daikin Ind Ltd | 2−フルオロフコシル−n−アロイルグルコサミン誘導体及びその中間物、並びにそれらの製造方法 |
TW480247B (en) | 1997-12-12 | 2002-03-21 | Gilead Sciences Inc | Novel compounds useful as neuraminidase inhibitors and pharmaceutical compositions containing same |
IT1298087B1 (it) | 1998-01-08 | 1999-12-20 | Fiderm S R L | Dispositivo per il controllo della profondita' di penetrazione di un ago, in particolare applicabile ad una siringa per iniezioni |
AU765703B2 (en) | 1998-03-27 | 2003-09-25 | Bruce J. Bryan | Luciferases, fluorescent proteins, nucleic acids encoding the luciferases and fluorescent proteins and the use thereof in diagnostics, high throughput screening and novelty items |
JP2002510481A (ja) | 1998-04-02 | 2002-04-09 | ジェネンテック・インコーポレーテッド | 抗体変異体及びその断片 |
ATE458007T1 (de) | 1998-04-20 | 2010-03-15 | Glycart Biotechnology Ag | Glykosylierungs-engineering von antikörpern zur verbesserung der antikörperabhängigen zellvermittelten zytotoxizität |
US6455571B1 (en) | 1998-04-23 | 2002-09-24 | Abbott Laboratories | Inhibitors of neuraminidases |
SI1308455T1 (sl) | 1998-05-06 | 2006-08-31 | Genentech Inc | Sestavek, ki obsega protitelesa anti-HER2 |
JP3773153B2 (ja) | 1998-05-29 | 2006-05-10 | 独立行政法人理化学研究所 | シアル酸誘導体 |
US6528286B1 (en) | 1998-05-29 | 2003-03-04 | Genentech, Inc. | Mammalian cell culture process for producing glycoproteins |
EP2306195A3 (en) | 1998-09-18 | 2012-04-25 | Massachusetts Institute of Technology | Biological applications of semiconductor nanocrystals |
FR2783523B1 (fr) | 1998-09-21 | 2006-01-20 | Goemar Lab Sa | Fuco-oligosaccharides, enzyme pour leur preparation a partir des fucanes, bacterie productrice de l'enzyme et applications des fuco-oligosaccharides a la protection des plantes |
US6696304B1 (en) | 1999-02-24 | 2004-02-24 | Luminex Corporation | Particulate solid phase immobilized protein quantitation |
AUPP913999A0 (en) | 1999-03-12 | 1999-04-01 | Biota Scientific Management Pty Ltd | Novel chemical compounds and their use |
US7090973B1 (en) | 1999-04-09 | 2006-08-15 | Oscient Pharmaceuticals Corporation | Nucleic acid sequences relating to Bacteroides fragilis for diagnostics and therapeutics |
US7854934B2 (en) | 1999-08-20 | 2010-12-21 | Sloan-Kettering Institute For Cancer Research | Glycoconjugates, glycoamino acids, intermediates thereto, and uses thereof |
JP2001131074A (ja) * | 1999-08-20 | 2001-05-15 | Inst Of Physical & Chemical Res | シアル酸誘導体を有効成分として含む医薬 |
US6824780B1 (en) | 1999-10-29 | 2004-11-30 | Genentech, Inc. | Anti-tumor antibody compositions and methods of use |
AUPQ422399A0 (en) * | 1999-11-24 | 1999-12-16 | University Of New South Wales, The | Method of screening transformed or transfected cells |
US6727356B1 (en) | 1999-12-08 | 2004-04-27 | Epoch Pharmaceuticals, Inc. | Fluorescent quenching detection reagents and methods |
US20020098513A1 (en) | 2000-02-17 | 2002-07-25 | Glycominds Ltd. | Combinatorial complex carbohydrate libraries and methods for the manufacture and uses thereof |
US7019129B1 (en) | 2000-05-09 | 2006-03-28 | Biosearch Technologies, Inc. | Dark quenchers for donor-acceptor energy transfer |
US7863020B2 (en) | 2000-06-28 | 2011-01-04 | Glycofi, Inc. | Production of sialylated N-glycans in lower eukaryotes |
US6514221B2 (en) | 2000-07-27 | 2003-02-04 | Brigham And Women's Hospital, Inc. | Blood-brain barrier opening |
US20020065259A1 (en) | 2000-08-30 | 2002-05-30 | Schatzberg Alan F. | Glucocorticoid blocking agents for increasing blood-brain barrier permeability |
AUPR001000A0 (en) | 2000-09-08 | 2000-10-05 | Biota Scientific Management Pty Ltd | Novel chemical compounds and their use |
US7034036B2 (en) | 2000-10-30 | 2006-04-25 | Pain Therapeutics, Inc. | Inhibitors of ABC drug transporters at the blood-brain barrier |
US20030083299A1 (en) | 2000-11-04 | 2003-05-01 | Ferguson Ian A. | Non-invasive delivery of polypeptides through the blood-brain barrier |
JP2002153272A (ja) | 2000-11-24 | 2002-05-28 | Inst Of Physical & Chemical Res | 生体分子マイクロアレイ |
US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
WO2002086096A2 (en) | 2001-01-23 | 2002-10-31 | University Of Rochester Medical Center | Methods of producing or identifying intrabodies in eukaryotic cells |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
DE10121982B4 (de) | 2001-05-05 | 2008-01-24 | Lts Lohmann Therapie-Systeme Ag | Nanopartikel aus Protein mit gekoppeltem Apolipoprotein E zur Überwindung der Blut-Hirn-Schranke und Verfahren zu ihrer Herstellung |
EP2147679B1 (en) | 2001-07-25 | 2014-06-25 | Raptor Pharmaceutical, Inc. | Compositions for blood-brain barrier transport |
EP1434859A2 (en) | 2001-07-25 | 2004-07-07 | New York University | Use of glycosylceramides as adjuvants for vaccines against infections and cancer |
CA2838062C (en) | 2001-08-03 | 2015-12-22 | Roche Glycart Ag | Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity |
DK1578771T3 (da) | 2001-10-10 | 2013-06-10 | Novo Nordisk As | Remodellering og glycokonjugering af peptider |
US7151164B2 (en) | 2002-02-14 | 2006-12-19 | Immunomedics, Inc. | Anti-CD20 antibodies and fusion proteins thereof and methods of use |
KR20040077655A (ko) | 2001-10-19 | 2004-09-06 | 슈페리어 마이크로파우더스 엘엘씨 | 전자 형상 증착용 테잎 조성물 |
AUPR879601A0 (en) | 2001-11-09 | 2001-12-06 | Biota Scientific Management Pty Ltd | Novel chemical compounds and their use |
US6873914B2 (en) | 2001-11-21 | 2005-03-29 | Icoria, Inc. | Methods and systems for analyzing complex biological systems |
US20030162695A1 (en) | 2002-02-27 | 2003-08-28 | Schatzberg Alan F. | Glucocorticoid blocking agents for increasing blood-brain barrier permeability |
US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
AU2003219277A1 (en) | 2002-03-14 | 2003-09-29 | Medical Research Council | Intracellular antibodies |
MXPA04011249A (es) | 2002-05-14 | 2005-06-06 | Chiron Srl | Vacunas mucosales con adyuvante de quitosano y antigenos meningococicos. |
RS20050006A (en) | 2002-07-08 | 2007-09-21 | Glaxo Smith Kline Istraživački Centar Zagreb D.O.O., | Novel compounds,compositions as carriers for steroid/non- steroid anti-inflammatory,antineoplastic and antiviral active molecules |
US20080070324A1 (en) | 2002-07-15 | 2008-03-20 | Floyd Alton D | Quantity control device for microscope slide staining assays |
EP1391213A1 (en) | 2002-08-21 | 2004-02-25 | Boehringer Ingelheim International GmbH | Compositions and methods for treating cancer using maytansinoid CD44 antibody immunoconjugates and chemotherapeutic agents |
US20040062682A1 (en) | 2002-09-30 | 2004-04-01 | Rakow Neal Anthony | Colorimetric sensor |
EP3284753B1 (en) | 2002-10-17 | 2019-06-05 | Genmab A/S | Human monoclonal antibodies against cd20 for use in the treatment of multiple sclerosis |
KR101111477B1 (ko) | 2002-12-03 | 2012-02-23 | 블랜체트 록펠러 뉴로사이언시즈 인스티튜트 | 치료제와 연결된 콜레스테롤을 포함하는 접합체 |
TWI335821B (en) | 2002-12-16 | 2011-01-11 | Genentech Inc | Immunoglobulin variants and uses thereof |
WO2004063351A2 (en) | 2003-01-09 | 2004-07-29 | Macrogenics, Inc. | IDENTIFICATION AND ENGINEERING OF ANTIBODIES WITH VARIANT Fc REGIONS AND METHODS OF USING SAME |
US8088387B2 (en) | 2003-10-10 | 2012-01-03 | Immunogen Inc. | Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates |
AR044388A1 (es) | 2003-05-20 | 2005-09-07 | Applied Molecular Evolution | Moleculas de union a cd20 |
US20040259142A1 (en) | 2003-06-04 | 2004-12-23 | Imperial College Innovations Limited | Products and methods |
EP2481814A3 (en) | 2003-06-09 | 2012-10-10 | The Regents of the University of Michigan | Compositions and methods for treating and diagnosing cancer |
JP4148844B2 (ja) | 2003-06-11 | 2008-09-10 | ソニー・エリクソン・モバイルコミュニケーションズ株式会社 | 情報端末装置及び音声付画像ファイルの出力方法 |
JP2007505142A (ja) | 2003-09-10 | 2007-03-08 | セダーズ−シナイ メディカル センター | 血液脳関門を通過する薬剤のカリウムチャネル媒介性送達 |
US20060286140A1 (en) | 2003-09-15 | 2006-12-21 | Eric Wickstrom | Implants with attached silylated therapeutic agents |
AU2004275770A1 (en) | 2003-09-22 | 2005-04-07 | Acidophil Llc | Small molecule compositions and methods for increasing drug efficiency using compositions thereof |
US7019288B2 (en) | 2003-09-30 | 2006-03-28 | Sequenom, Inc. | Methods of making substrates for mass spectrometry analysis and related devices |
US20050221337A1 (en) | 2003-10-02 | 2005-10-06 | Massachusetts Institute Of Technology | Microarrays and microspheres comprising oligosaccharides, complex carbohydrates or glycoproteins |
WO2005044859A2 (en) | 2003-11-05 | 2005-05-19 | Glycart Biotechnology Ag | Cd20 antibodies with increased fc receptor binding affinity and effector function |
SI1725249T1 (sl) | 2003-11-06 | 2014-04-30 | Seattle Genetics, Inc. | Spojine monometilvalina, sposobne konjugacije na ligande |
US20050255491A1 (en) | 2003-11-13 | 2005-11-17 | Lee Frank D | Small molecule and peptide arrays and uses thereof |
EP1723422A2 (en) | 2004-03-05 | 2006-11-22 | The Scripps Research Institute | High throughput glycan microarrays |
US20050221397A1 (en) | 2004-03-30 | 2005-10-06 | Northern Advancement Center For Science & Technology | RM2 antigen (beta1,4-GalNAc-disialyl-Lc4) as prostate cancer-associated antigen |
WO2005103081A2 (en) | 2004-04-20 | 2005-11-03 | Genmab A/S | Human monoclonal antibodies against cd20 |
ITMI20040928A1 (it) | 2004-05-07 | 2004-08-07 | Uni Di Bologna Dipartiment O D | Procedura per la preparazione di coniugati della doxorubicina con l'albumina umana lattosaminata |
WO2006002382A2 (en) | 2004-06-24 | 2006-01-05 | The Scripps Research Institute | Arrays with cleavable linkers |
JP2008507520A (ja) | 2004-07-22 | 2008-03-13 | ジェネンテック・インコーポレーテッド | Her2抗体組成物 |
US8022043B2 (en) | 2004-08-27 | 2011-09-20 | Albert Einstein College Of Medicine Of Yeshiva University | Ceramide derivatives as modulators of immunity and autoimmunity |
WO2006055925A2 (en) | 2004-11-19 | 2006-05-26 | Swiss Federal Institute Of Technology | Microarrays for analyte detection |
WO2006064983A1 (en) | 2004-12-14 | 2006-06-22 | Korea Research Institute Of Bioscience And Biotechnology | Monoclonal antibody specific human embryonic stem cell |
US7923013B2 (en) | 2004-12-28 | 2011-04-12 | The Rockefeller University | Glycolipids and analogues thereof as antigens for NKT cells |
JP5090928B2 (ja) | 2004-12-28 | 2012-12-05 | ザ ロックフェラー ユニバーシティ | Nkt細胞に対する抗原としての糖脂質及びその類似体 |
TWI381050B (zh) | 2005-03-31 | 2013-01-01 | Biomedics Inc | Anti-CD20 monoclonal antibody |
MX2007014673A (es) | 2005-05-24 | 2008-04-08 | Avestha Gengraine Tech Pvt Ltd | Metodo para la produccion de un anticuerpo monoclonal para cd20 para el tratamiento de linfoma de celular b. |
AU2006252733A1 (en) | 2005-06-02 | 2006-12-07 | Astrazeneca Ab | Antibodies directed to CD20 and uses thereof |
JP5228190B2 (ja) * | 2005-11-14 | 2013-07-03 | 国立大学法人 東京大学 | パーオキシナイトライト蛍光プローブ |
US7781203B2 (en) | 2005-12-29 | 2010-08-24 | Corning Incorporated | Supports for assaying analytes and methods of making and using thereof |
EP2001358B1 (en) | 2006-03-27 | 2016-07-13 | University Of Maryland, Baltimore | Glycoprotein synthesis and remodeling by enzymatic transglycosylation |
KR20090031362A (ko) | 2006-05-18 | 2009-03-25 | 페터리내르메디찌니쉐 우니버지태트 빈 | 인플루엔자 바이러스의 검출 방법 |
US20100173323A1 (en) | 2006-06-09 | 2010-07-08 | University Of Maryland, Baltimore | Glycosylation engineered antibody therapy |
EP2052250B1 (en) | 2006-07-12 | 2012-05-16 | Merck Patent GmbH | Solid-phase detection of terminal monosaccharides cleaved from glycosylated substrates |
JP2010501161A (ja) | 2006-08-18 | 2010-01-21 | オンコセラピー・サイエンス株式会社 | Reg4またはkiaa0101を過剰発現している癌の治療または予防 |
JP5391073B2 (ja) | 2006-11-27 | 2014-01-15 | ディアデクサス インコーポレーテッド | Ovr110抗体組成物および使用方法 |
WO2008087257A1 (en) | 2007-01-18 | 2008-07-24 | Suomen Punainen Risti, Veripalvelu | Novel methods and reagents directed to production of cells |
US20100047827A1 (en) | 2007-01-18 | 2010-02-25 | Suomen Punainen Risti, Veripalvelu | Novel specific cell binders |
DK2123271T3 (da) | 2007-03-07 | 2012-01-23 | Daiichi Sankyo Co Ltd | Lægemiddel til behandling af influenza |
US20080220988A1 (en) | 2007-03-07 | 2008-09-11 | Ada Technologies, Inc. | Preparing carbohydrate microarrays and conjugated nanoparticles |
US7960139B2 (en) | 2007-03-23 | 2011-06-14 | Academia Sinica | Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells |
US7943330B2 (en) | 2007-03-23 | 2011-05-17 | Academia Sinica | Tailored glycoproteomic methods for the sequencing, mapping and identification of cellular glycoproteins |
EP2125024B1 (en) | 2007-03-23 | 2013-02-13 | TO-BBB Holding B.V. | Targeted intracellular delivery of antiviral agents |
US20080260774A1 (en) | 2007-04-13 | 2008-10-23 | Chi-Huey Wong | Alpha-galactosyl ceramide analogs and their use as immunotherapies |
CN101986783A (zh) | 2007-04-23 | 2011-03-16 | 先灵公司 | 抗mdl-1抗体 |
CA2697508A1 (en) | 2007-08-24 | 2009-03-05 | Tokyo Institute Of Technology | Method for detecting gynecologic cancer |
CN101883569B (zh) | 2007-08-31 | 2013-08-21 | 梁启铭 | 具有抗流感活性之含奥司他伟膦酸酯同系物的合成 |
FR2921387B1 (fr) | 2007-09-26 | 2012-04-20 | Sanofi Pasteur | Procede de production du virus de la grippe |
US8647626B2 (en) | 2007-10-02 | 2014-02-11 | Avaxia Biologics, Incorporated | Compositions comprising TNF-specific antibodies for oral delivery |
US20090123439A1 (en) | 2007-11-09 | 2009-05-14 | The Jackson Laboratory | Diagnostic and prognosis methods for cancer stem cells |
EP2225276B1 (en) | 2007-12-31 | 2014-04-23 | Bayer Intellectual Property GmbH | Antibodies to tnf alpha |
RU2536256C2 (ru) | 2008-03-21 | 2014-12-20 | ДАНИСКО ЮЭс ИНК. | Композиция ферментной смеси для гидролиза смеси целлюлозных и гемицеллюлозных материалов (варианты) и способы ее использования (варианты) |
EP2272854B1 (en) | 2008-03-25 | 2015-08-05 | Riken | Novel glycolipid and use thereof |
US8383554B2 (en) | 2008-04-14 | 2013-02-26 | Academia Sinica | Quantitative microarray of intact glycolipid CD1d interaction and correlation with cell-based cytokine production |
US8906832B2 (en) | 2008-04-30 | 2014-12-09 | Academia Sinica | Quantitative analysis of carbohydrate-protein interactions using glycan microarrays: determination of surface and solution dissociation constants |
CN105363034A (zh) | 2008-05-23 | 2016-03-02 | 香港大学 | 治疗流感的联合疗法 |
WO2009154964A2 (en) | 2008-05-30 | 2009-12-23 | Glycome Technologies Inc. | Methods for structural analysis of glycans |
WO2010008736A2 (en) | 2008-06-16 | 2010-01-21 | Academia Sinica | Cancer diagnosis based on levels of antibodies against globo h and its fragments |
AU2009268937A1 (en) | 2008-06-16 | 2010-01-14 | Aj Park | Compositions for inducing immune responses specific to Globo H and SSEA3 and uses thereof in cancer treatment |
JP2010014691A (ja) | 2008-06-20 | 2010-01-21 | Igaku Seibutsugaku Kenkyusho:Kk | 腹水中のメソテリン及び/又は巨核球増強因子を検出するための方法、キット、試薬及び装置 |
US7928077B2 (en) | 2008-07-11 | 2011-04-19 | Academia Sinica | Alpha-galactosyl ceramide analogs and their use as immunotherapies |
EP2318832B1 (en) | 2008-07-15 | 2013-10-09 | Academia Sinica | Glycan arrays on ptfe-like aluminum coated glass slides and related methods |
US20100022916A1 (en) | 2008-07-24 | 2010-01-28 | Javanbakhsh Esfandiari | Method and Apparatus for Collecting and Preparing Biological Samples for Testing |
EP2411528B1 (en) | 2009-03-27 | 2015-09-02 | Academia Sinica | Alpha-selective sialyl phosphate donors for preparation of sialosides and sialoside arrays for influenza virus detection |
CA2768155C (en) * | 2009-06-16 | 2016-08-23 | The University Of Bath | Materials and methods relating to glycosylation |
WO2011005756A1 (en) | 2009-07-06 | 2011-01-13 | Puretech Ventures, Llc | Delivery of agents targeted to microbiota niches |
CA2767453C (en) | 2009-07-15 | 2018-10-09 | The University Of British Columbia | Neuraminidase inhibitor compounds, compositions and methods for the use thereof as anti-virals |
CN102481364A (zh) | 2009-07-22 | 2012-05-30 | 安龙制药公司 | 用her2受体拮抗剂联合7-乙基-10-羟基喜树碱的多臂聚合缀合物治疗her2阳性癌症的方法 |
US20120172329A1 (en) | 2009-09-14 | 2012-07-05 | Thailand Excellence Center For Tissue Engineering | Phytochemical compositions including xanthones for anti-inflammatory, anti-cytokine storm, and other uses |
US10087236B2 (en) | 2009-12-02 | 2018-10-02 | Academia Sinica | Methods for modifying human antibodies by glycan engineering |
WO2011074621A1 (ja) | 2009-12-18 | 2011-06-23 | 株式会社医学生物学研究所 | メソセリン(msln)に対する抗体及びその用途 |
EP2347769A1 (en) | 2010-01-20 | 2011-07-27 | Glycotope GmbH | Cancer stem cell markers and uses thereof |
NZ601580A (en) | 2010-02-11 | 2014-11-28 | Alexion Pharma Inc | Therapeutic methods using anti-cd200 antibodies |
AR080513A1 (es) | 2010-03-12 | 2012-04-11 | Inmunogen Inc | Moleculas de union cd37 y sus inmunoconjugados |
US10338069B2 (en) | 2010-04-12 | 2019-07-02 | Academia Sinica | Glycan arrays for high throughput screening of viruses |
CA2796464C (en) | 2010-04-16 | 2021-08-03 | Immune Disease Institute, Inc. | Sustained polypeptide expression from synthetic, modified rnas and uses thereof |
KR101745386B1 (ko) | 2010-05-10 | 2017-06-09 | 아카데미아 시니카 | 항-인플루엔자 활성을 가진 자나미비르 포스포네이트 동족체 및 인플루엔자 바이러스의 오셀타미비르 감수성을 확인하는 방법 |
WO2011145957A1 (en) * | 2010-05-20 | 2011-11-24 | Auckland Uniservices Limited | Agents and methods for detection and/or imaging of hypoxia |
BR112012030179A8 (pt) | 2010-05-27 | 2023-03-14 | Merck Sharp & Dohme | Polipeptídeo contendo fc |
GB201015569D0 (en) | 2010-09-16 | 2010-10-27 | Medical Res Council | Blood assay for prions |
WO2012082635A1 (en) | 2010-12-13 | 2012-06-21 | Ancora Pharmaceuticals, Inc. | Synthetic oligosaccharide group a streptococcus |
JP6057300B2 (ja) | 2011-01-05 | 2017-01-11 | ナショナル タイワン ユニバーシティ | グリコスフィンゴ脂質の調製及びその使用の方法 |
US10851174B2 (en) | 2011-03-03 | 2020-12-01 | University Of Maryland, Baltimore | Core fucosylated glycopeptides and glycoproteins: chemoenzymatic synthesis and uses thereof |
AU2012258907A1 (en) | 2011-05-25 | 2013-11-07 | Merck Sharp & Dohme Corp. | Method for preparing Fc-containing polypeptides having improved properties |
WO2013012754A1 (en) * | 2011-07-15 | 2013-01-24 | University Of Southern California | Boron-based dual imaging probes, compositions and methods for rapid aqueous f-18 labeling, and imaging methods using same |
DK3418300T3 (da) | 2011-07-18 | 2020-12-07 | Inst Res Biomedicine | Neutralisering af anti-influenza-a-virusantistoffer og anvendelser deraf |
US9216999B2 (en) * | 2011-08-12 | 2015-12-22 | Nissan Chemical Industries, Ltd. | Substituted pyrrolo[2,3-h][1,6]naphthyridines and compositions thereof as JAK inhibitors |
US20140302028A1 (en) | 2011-11-18 | 2014-10-09 | Merck Sharp & Dohme Corp. | Fc containing polypeptides having increased anti-inflammatory properties and increased fcrn binding |
EP2604281B1 (en) * | 2011-12-14 | 2014-07-30 | Centre National de la Recherche Scientifique (CNRS) | Clicked somatostatin conjugated analogs for biological applications |
CA2862925C (en) | 2012-02-10 | 2020-01-21 | University Of Maryland, Baltimore | Chemoenzymatic glycoengineering of antibodies and fc fragments thereof |
WO2013130603A1 (en) | 2012-02-27 | 2013-09-06 | Board Of Regents, The University Of Texas System | Ganglioside gd2 as a marker and target on cancer stem cells |
AU2013243584A1 (en) | 2012-04-02 | 2014-10-09 | Merrimack Pharmaceuticals, Inc. | Dosage and administration of monospecific and bispecific anti-IGF-1R and anti-ErbB3 antibodies |
WO2013151649A1 (en) | 2012-04-04 | 2013-10-10 | Sialix Inc | Glycan-interacting compounds |
US10130714B2 (en) | 2012-04-14 | 2018-11-20 | Academia Sinica | Enhanced anti-influenza agents conjugated with anti-inflammatory activity |
WO2013181585A2 (en) | 2012-06-01 | 2013-12-05 | Momenta Pharmaceuticals, Inc. | Methods related to adalimumab |
US9914956B2 (en) * | 2012-08-18 | 2018-03-13 | Academia Sinica | Cell-permeable probes for identification and imaging of sialidases |
TWI563091B (en) | 2012-08-20 | 2016-12-21 | Academia Sinica | Large scale enzymatic synthesis of oligosaccharides |
WO2014031762A1 (en) * | 2012-08-21 | 2014-02-27 | Academia Sinica | Benzocyclooctyne compounds and uses thereof |
DK2914633T3 (da) | 2012-10-30 | 2022-03-14 | Esperance Pharmaceuticals Inc | Antistof/lægemiddel-konjugater og anvendelsesfremgangsmåder |
US20150284452A1 (en) | 2012-11-13 | 2015-10-08 | Iogenetics, Llc | Antimicrobial compositions |
EP3013365B1 (en) | 2013-06-26 | 2019-06-05 | Academia Sinica | Rm2 antigens and use thereof |
WO2014210564A1 (en) | 2013-06-27 | 2014-12-31 | Academia Sinica | Glycan conjugates and use thereof |
TWI599370B (zh) | 2013-07-26 | 2017-09-21 | 中央研究院 | 靈芝多醣誘發之抗體介導抗腫瘤活性 |
US9782476B2 (en) | 2013-09-06 | 2017-10-10 | Academia Sinica | Human iNKT cell activation using glycolipids with altered glycosyl groups |
US20160201132A1 (en) | 2013-09-12 | 2016-07-14 | Teva Pharmaceutical Industries Ltd. | Gene expression biomarkers of laquinimod responsiveness |
WO2015054039A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Fc CONTAINING POLYPEPTIDES HAVING INCREASED BINDING TO FcGammaRIIB |
US10150818B2 (en) | 2014-01-16 | 2018-12-11 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
JP2017507118A (ja) | 2014-01-16 | 2017-03-16 | アカデミア シニカAcademia Sinica | がんの処置および検出のための組成物および方法 |
TWI687428B (zh) | 2014-03-27 | 2020-03-11 | 中央研究院 | 反應性標記化合物及其用途 |
KR102512592B1 (ko) | 2014-05-27 | 2023-03-21 | 아카데미아 시니카 | 항-her2 글리코항체 및 이의 용도 |
CA2950415A1 (en) | 2014-05-27 | 2015-12-03 | Academia Sinica | Anti-cd20 glycoantibodies and uses thereof |
US10118969B2 (en) | 2014-05-27 | 2018-11-06 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
EP3149045B1 (en) | 2014-05-27 | 2023-01-18 | Academia Sinica | Compositions and methods relating to universal glycoforms for enhanced antibody efficacy |
KR102494193B1 (ko) | 2014-05-28 | 2023-01-31 | 아카데미아 시니카 | 항-tnf-알파 글리코항체 및 이의 용도 |
MX2017002333A (es) | 2014-08-22 | 2017-08-28 | Academia Sinica | Conjugados novedosos de glicano y uso de los mismos. |
KR102422375B1 (ko) | 2014-09-08 | 2022-07-18 | 아카데미아 시니카 | 당지질을 사용한 인간 iNKT 세포 활성화 |
US10495645B2 (en) | 2015-01-16 | 2019-12-03 | Academia Sinica | Cancer markers and methods of use thereof |
US9975965B2 (en) | 2015-01-16 | 2018-05-22 | Academia Sinica | Compositions and methods for treatment and detection of cancers |
WO2016118090A1 (en) | 2015-01-23 | 2016-07-28 | Agency For Science, Technology And Research | Cancer specific antigen-binding proteins |
US20170283878A1 (en) | 2015-12-11 | 2017-10-05 | Academia Sinica | Modulation of globoseries glycosphingolipid synthesis and cancer biomarkers |
-
2015
- 2015-03-27 TW TW104110104A patent/TWI687428B/zh active
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- 2015-03-27 CN CN201580016671.XA patent/CN106415244B/zh active Active
- 2015-03-27 JP JP2016558730A patent/JP6562942B2/ja active Active
- 2015-03-27 EP EP15770237.4A patent/EP3129767B1/en active Active
- 2015-03-27 WO PCT/US2015/022977 patent/WO2015148915A1/en active Application Filing
- 2015-04-28 US US14/698,660 patent/US9759726B2/en active Active
-
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- 2017-08-01 US US15/666,242 patent/US10119972B2/en active Active
-
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- 2019-07-23 JP JP2019135289A patent/JP6884177B2/ja active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20140051109A1 (en) * | 2011-03-01 | 2014-02-20 | Agency For Science, Technology And Research | Novel compounds with photoluminescence properties and applications thereof |
Non-Patent Citations (9)
Title |
---|
BAI,D. ET AL.: "Exploring Forester electronic energy transfer in a decoupled anthracenyl-based borondipyrromethene (", PHYSICAL CHEMISTRY CHEMICAL PHYSICS, vol. 14, no. 13, JPN6018040679, 2012, pages 4447 - 4456 * |
BRYDEN,F. ET AL.: "A mild, facile, one-pot synthesis of zinc azido porphyrins as substrates for use in click chemistry", SYNLETT, vol. 24, no. 15, JPN6018040691, 2013, pages 1978 - 1982 * |
HAN,J. ET AL.: "3- and 5-Functionalized BODIPYs via the Liebeskind-Srogl reaction", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 7, no. 1, JPN7018003542, 2009, pages 34 - 36, XP055054319, DOI: doi:10.1039/B818390B * |
JOSE,J. ET AL.: "Energy transfer dyads based on Nile Red", TETRAHEDRON LETTERS, vol. 50, no. 47, JPN6018040681, 2009, pages 6442 - 6445, XP026673569, DOI: doi:10.1016/j.tetlet.2009.08.130 * |
LEONARDI,M.J. ET AL.: "Efficient Foerster Resonance Energy Transfer in 1,2,3-Triazole Linked BODIPY-Zn(II) Meso-tetraphenyl", INORGANIC CHEMISTRY, vol. 51, no. 24, JPN6018040677, 2012, pages 13114 - 13122 * |
LI,L. ET AL.: "Syntheses and spectral properties of functionalized, water-soluble BODIPY derivatives", JOURNAL OF ORGANIC CHEMISTRY, vol. 73, no. 5, JPN6018040685, 2008, pages 1963 - 1970, XP055024838, DOI: doi:10.1021/jo702463f * |
SHIE,J. ET AL.: "An Azido-BODIPY Probe for Glycosylation: Initiation of Strong Fluorescence upon Triazole Formation", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 136, no. 28, JPN6018040676, 2014, pages 9953 - 9961 * |
SHIEH,P. ET AL.: "Fluorogenic Azidofluoresceins for Biological Imaging", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 134, no. 42, JPN6018040688, 2012, pages 17428 - 17431 * |
WU,L. ET AL.: "Fluorescent Cassettes for Monitoring Three-Component Interactions in Vitro and in Living Cells", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 131, no. 26, JPN6018040683, 2009, pages 9156 - 9157, XP002547575, DOI: doi:10.1021/ja9029413 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020139782A (ja) * | 2019-02-27 | 2020-09-03 | 公立大学法人福井県立大学 | 生体高分子を認識するハイブリッド型蛍光プローブ |
JP7264344B2 (ja) | 2019-02-27 | 2023-04-25 | 公立大学法人福井県立大学 | 生体高分子を認識するハイブリッド型蛍光プローブ |
JP7498468B2 (ja) | 2019-02-27 | 2024-06-12 | 公立大学法人福井県立大学 | 生体高分子を認識するハイブリッド型蛍光プローブ |
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EP3129767B1 (en) | 2021-09-01 |
JP2020002139A (ja) | 2020-01-09 |
JP6884177B2 (ja) | 2021-06-09 |
WO2015148915A1 (en) | 2015-10-01 |
WO2015148915A9 (en) | 2016-12-22 |
TW202026300A (zh) | 2020-07-16 |
US9759726B2 (en) | 2017-09-12 |
US20180011104A1 (en) | 2018-01-11 |
TWI687428B (zh) | 2020-03-11 |
US20150309041A1 (en) | 2015-10-29 |
US10119972B2 (en) | 2018-11-06 |
EP3129767A1 (en) | 2017-02-15 |
TWI797430B (zh) | 2023-04-01 |
EP3129767A4 (en) | 2018-01-10 |
CN106415244A (zh) | 2017-02-15 |
CN106415244B (zh) | 2020-04-24 |
JP6562942B2 (ja) | 2019-08-28 |
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