CA3077662A1 - Methods for tagging dna-encoded libraries - Google Patents
Methods for tagging dna-encoded librariesInfo
- Publication number
- CA3077662A1 CA3077662A1 CA3077662A CA3077662A CA3077662A1 CA 3077662 A1 CA3077662 A1 CA 3077662A1 CA 3077662 A CA3077662 A CA 3077662A CA 3077662 A CA3077662 A CA 3077662A CA 3077662 A1 CA3077662 A1 CA 3077662A1
- Authority
- CA
- Canada
- Prior art keywords
- building block
- tag
- headpiece
- nucleotides
- group
- 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.)
- Abandoned
Links
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1065—Preparation or screening of tagged libraries, e.g. tagged microorganisms by STM-mutagenesis, tagged polynucleotides, gene tags
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1068—Template (nucleic acid) mediated chemical library synthesis, e.g. chemical and enzymatical DNA-templated organic molecule synthesis, libraries prepared by non ribosomal polypeptide synthesis [NRPS], DNA/RNA-polymerase mediated polypeptide synthesis
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
- C12N15/1034—Isolating an individual clone by screening libraries
- C12N15/1093—General methods of preparing gene libraries, not provided for in other subgroups
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- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B50/00—Methods of creating libraries, e.g. combinatorial synthesis
- C40B50/14—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
- C40B50/16—Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support involving encoding steps
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/11—Compounds covalently bound to a solid support
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| CN101006177B (zh) * | 2002-03-15 | 2011-10-12 | 纽韦卢森公司 | 改善的用于合成模制分子的方法 |
| EP3216874A1 (en) | 2008-09-05 | 2017-09-13 | TOMA Biosciences, Inc. | Methods for stratifying and annotating cancer drug treatment options |
| WO2010094036A1 (en) | 2009-02-13 | 2010-08-19 | X-Chem, Inc. | Methods of creating and screening dna-encoded libraries |
| KR20130113447A (ko) | 2010-09-24 | 2013-10-15 | 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 | 고정된 프라이머들을 이용하여 표적 dna의 직접적인 캡쳐, 증폭 및 서열화 |
| SG10201605812YA (en) | 2011-09-07 | 2016-09-29 | Chem Inc X | Methods for tagging dna-encoded libraries |
| KR102146721B1 (ko) * | 2012-07-13 | 2020-08-21 | 엑스-켐, 인크. | 폴리머라제에 의해 판독가능하지 않은 코딩 올리고뉴클레오티드 연결을 갖는 dna-코딩된 라이브러리 |
| US20140179560A1 (en) | 2012-12-10 | 2014-06-26 | Fred Hutchinson Cancer Research Center | Drug discovery methods and platforms |
| CA2891966A1 (en) * | 2012-12-20 | 2014-06-26 | Sirna Therapeutics, Inc. | Post-synthetic orthogonal amidation plus metal catalyzed azide-alkyne cycloaddition click chemistry on sirna |
| CN103882532B (zh) * | 2012-12-20 | 2015-10-21 | 成都先导药物开发有限公司 | 一种先导化合物的合成及筛选方法与试剂盒 |
| GB201322692D0 (en) | 2013-12-20 | 2014-02-05 | Philochem Ag | Production of encoded chemical libraries |
| GB201404552D0 (en) * | 2014-03-14 | 2014-04-30 | Philochem Ag | Purification of dna-conjugate products |
| US10900065B2 (en) | 2014-11-14 | 2021-01-26 | University Of Washington | Methods and kits for labeling cellular molecules |
| MA41298A (fr) * | 2014-12-30 | 2017-11-07 | X Chem Inc | Procédés de marquage de banques codées par de l'adn |
| CN104894651B (zh) * | 2015-06-29 | 2017-04-12 | 天津诺禾医学检验所有限公司 | 微量起始dna的高通量测序文库构建方法及其所构建的高通量测序文库 |
| WO2017218293A1 (en) * | 2016-06-16 | 2017-12-21 | Richard Edward Watts | Oligonucleotide directed and recorded combinatorial synthesis of encoded probe molecules |
| CN107130300A (zh) * | 2016-10-08 | 2017-09-05 | 深圳劲宇生物科技有限公司 | 一种dna编码分子库的合成方法及dna模板 |
| WO2018107093A1 (en) * | 2016-12-09 | 2018-06-14 | University Of Southern California | Genome-wide mapping of dna-dna proximities in the nucleus |
| EP3360962A1 (en) * | 2017-02-14 | 2018-08-15 | Technische Universität Dortmund | Synthesis of dna-encoded libraries by micellar catalysis |
| CN110325491B (zh) | 2017-03-17 | 2022-04-19 | 成都先导药物开发股份有限公司 | 编码库的合成方法及组合物 |
| WO2018204420A1 (en) * | 2017-05-02 | 2018-11-08 | Haystack Sciences Corporation | Molecules for verifying oligonucleotide directed combinatorial synthesis and methods of making and using the same |
| US20210404007A1 (en) * | 2017-06-30 | 2021-12-30 | The Regents Of The University Of California | Methods and systems for evaluating dna methylation in cell-free dna |
| US20200263163A1 (en) * | 2017-09-25 | 2020-08-20 | Haystack Sciences Corporation | Multinomial encoding for oligonucleotide-directed combinatorial chemistry |
| CN108070009B (zh) * | 2017-12-12 | 2021-04-13 | 上海药明康德新药开发有限公司 | 一种制备dna编码化合物文库的方法及起始头片段化合物和制得的dna编码化合物 |
| TW201940695A (zh) * | 2018-01-12 | 2019-10-16 | 英商卡美納生物科學公司 | 用於無模板幾何型酶催化性核酸合成之組成物和方法 |
| WO2019149198A1 (zh) * | 2018-01-31 | 2019-08-08 | 成都先导药物开发股份有限公司 | 一种dna编码化合物库及化合物筛选方法 |
| WO2019157692A1 (zh) * | 2018-02-14 | 2019-08-22 | 深圳劲宇生物科技有限公司 | Dna 编码分子库及无靶点限制的化合物筛选方法 |
| WO2019157693A1 (zh) * | 2018-02-14 | 2019-08-22 | 深圳劲宇生物科技有限公司 | Dna编码分子库及应用广的化合物筛选方法 |
| EP4647508A2 (en) | 2018-04-02 | 2025-11-12 | Enumera Molecular, Inc. | Methods, systems, and compositions for counting nucleic acid molecules |
| CN110658163A (zh) * | 2018-06-29 | 2020-01-07 | 成都先导药物开发股份有限公司 | 一种合成dna编码化合物中的反应监测方法 |
| CN109468310B (zh) * | 2018-10-25 | 2020-12-01 | 深圳劲宇生物科技有限公司 | Dna编码碎片分子库的合成方法和连接基团的筛选方法 |
| EP3899521A4 (en) | 2018-12-20 | 2022-08-24 | Sergey N. Krylov | SELECTION OF BINDERS USING CAPILLARY ELECTROPHORESIS |
| JP7537422B2 (ja) * | 2019-02-18 | 2024-08-21 | 味の素株式会社 | 相補部分を含む修飾オリゴヌクレオチドの製造方法 |
| EP3947718A4 (en) | 2019-04-02 | 2022-12-21 | Enumera Molecular, Inc. | METHODS, SYSTEMS AND COMPOSITIONS FOR COUNTING NUCLEIC ACID MOLECULES |
| JP7651470B2 (ja) * | 2019-04-05 | 2025-03-26 | クラレット バイオサイエンス， エルエルシー | 核酸を解析するための方法および組成物 |
| CN113811610A (zh) * | 2019-05-09 | 2021-12-17 | 加利福尼亚太平洋生物科学股份有限公司 | 用于改进cDNA合成的组合物和方法 |
| EP4004202A1 (en) * | 2019-07-25 | 2022-06-01 | X-Chem, Inc. | Methods for tagging and encoding of pre-existing compound libraries |
| WO2023077001A1 (en) * | 2021-10-27 | 2023-05-04 | Juan Pablo Maianti | Dna-encoded and affinity-tagged masked-warhead compounds and use thereof in assembling libraries of small molecules enabled for late-stage purification and multiplexed screening of covalent ligands |
| WO2024069235A2 (en) | 2022-09-30 | 2024-04-04 | Sixfold Bioscience Ltd. | Compositions containing oligonucleotides with theranostic applications |
| WO2025042899A2 (en) * | 2023-08-24 | 2025-02-27 | X-Chem, Inc. | Methods for identifying compounds binding to a target molecule using mirror-imaging of the target molecule |
| KR102774172B1 (ko) * | 2023-10-25 | 2025-02-28 | 서울대학교산학협력단 | Rna 변형의 모든 주변 서열을 포함하는 광범위한 rna 변형 라이브러리 설계법 및 그 이용 |
| US20250320488A1 (en) * | 2024-04-12 | 2025-10-16 | Insitro, Inc. | Methods of preparing oligonucleotide-directed combinatorial libraries |
Family Cites Families (161)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0260032B1 (en) * | 1986-09-08 | 1994-01-26 | Ajinomoto Co., Inc. | Compounds for the cleavage at a specific position of RNA, oligomers employed for the formation of said compounds, and starting materials for the synthesis of said oligomers |
| US5585481A (en) | 1987-09-21 | 1996-12-17 | Gen-Probe Incorporated | Linking reagents for nucleotide probes |
| US5025388A (en) | 1988-08-26 | 1991-06-18 | Cramer Richard D Iii | Comparative molecular field analysis (CoMFA) |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| US6005087A (en) * | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US5723289A (en) | 1990-06-11 | 1998-03-03 | Nexstar Pharmaceuticals, Inc. | Parallel selex |
| US5660985A (en) | 1990-06-11 | 1997-08-26 | Nexstar Pharmaceuticals, Inc. | High affinity nucleic acid ligands containing modified nucleotides |
| JP2780572B2 (ja) | 1991-09-13 | 1998-07-30 | 株式会社島津製作所 | オリゴヌクレオチドの酵素的合成法及びオリゴヌクレオチドのプライマーとしての使用 |
| US5639603A (en) | 1991-09-18 | 1997-06-17 | Affymax Technologies N.V. | Synthesizing and screening molecular diversity |
| CA2118806A1 (en) | 1991-09-18 | 1993-04-01 | William J. Dower | Method of synthesizing diverse collections of oligomers |
| US5573905A (en) | 1992-03-30 | 1996-11-12 | The Scripps Research Institute | Encoded combinatorial chemical libraries |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| CA2143848C (en) | 1992-10-01 | 2007-09-11 | W. Clark Still | Complex combinatorial chemical libraries encoded with tags |
| US6503759B1 (en) | 1992-10-01 | 2003-01-07 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
| US5807683A (en) | 1992-11-19 | 1998-09-15 | Combichem, Inc. | Combinatorial libraries and methods for their use |
| AU684279B2 (en) | 1993-04-12 | 1997-12-11 | Northwestern University | Method of forming oligonucleotides |
| US5681943A (en) | 1993-04-12 | 1997-10-28 | Northwestern University | Method for covalently linking adjacent oligonucleotides |
| US5840485A (en) | 1993-05-27 | 1998-11-24 | Selectide Corporation | Topologically segregated, encoded solid phase libraries |
| DK0705279T3 (da) | 1993-05-27 | 2003-06-10 | Selectide Corp | Topologisk adskilte, kodende fastfase-biblioteker |
| WO1995001365A1 (en) | 1993-07-02 | 1995-01-12 | Lynx Therapeutics, Inc. | Synthesis of branched nucleic acids |
| US5571903A (en) | 1993-07-09 | 1996-11-05 | Lynx Therapeutics, Inc. | Auto-ligating oligonucleotide compounds |
| US6087186A (en) | 1993-07-16 | 2000-07-11 | Irori | Methods and apparatus for synthesizing labeled combinatorial chemistry libraries |
| GB9315847D0 (en) | 1993-07-30 | 1993-09-15 | Isis Innovation | Tag reagent and assay method |
| DK96093D0 (da) | 1993-08-25 | 1993-08-25 | Symbicom Ab | Improvements in molecular modelling and drug design |
| US5658782A (en) | 1993-10-20 | 1997-08-19 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education On Behalf Of The Oregon Health Sciences University A Non-Profit Organization | Amino acid transporters and uses |
| NZ276860A (en) | 1993-11-02 | 1997-09-22 | Affymax Tech Nv | Apparatus and its use for synthesising diverse molecular products on substrates |
| US6117976A (en) | 1993-11-04 | 2000-09-12 | Medical Research Council | Manufacture and use of polypeptides tagged using binding molecules |
| AU692212B2 (en) | 1993-12-17 | 1998-06-04 | Roger S. Cubicciotti | Nucleotide-directed assembly of bimolecular and multimolecular drugs and devices |
| US6936477B2 (en) | 1994-04-13 | 2005-08-30 | The Trustees Of Columbia University In The City Of New York | Complex combinatorial chemical libraries encoded with tags |
| JPH08268A (ja) | 1994-06-16 | 1996-01-09 | Koichi Nishigaki | 連結した２本鎖ｄｎａの製造方法 |
| US5525734A (en) | 1994-06-22 | 1996-06-11 | Affymax Technologies N.V. | Methods for synthesizing diverse collections of pyrrolidine compounds |
| US5525735A (en) | 1994-06-22 | 1996-06-11 | Affymax Technologies Nv | Methods for synthesizing diverse collections of pyrrolidine compounds |
| AU697920B2 (en) | 1994-07-26 | 1998-10-22 | Scripps Research Institute, The | Soluble combinatorial libraries |
| US6406848B1 (en) | 1997-05-23 | 2002-06-18 | Lynx Therapeutics, Inc. | Planar arrays of microparticle-bound polynucleotides |
| US5604097A (en) | 1994-10-13 | 1997-02-18 | Spectragen, Inc. | Methods for sorting polynucleotides using oligonucleotide tags |
| US6654505B2 (en) | 1994-10-13 | 2003-11-25 | Lynx Therapeutics, Inc. | System and apparatus for sequential processing of analytes |
| US6013445A (en) | 1996-06-06 | 2000-01-11 | Lynx Therapeutics, Inc. | Massively parallel signature sequencing by ligation of encoded adaptors |
| USRE43097E1 (en) | 1994-10-13 | 2012-01-10 | Illumina, Inc. | Massively parallel signature sequencing by ligation of encoded adaptors |
| US5846719A (en) | 1994-10-13 | 1998-12-08 | Lynx Therapeutics, Inc. | Oligonucleotide tags for sorting and identification |
| US5695934A (en) | 1994-10-13 | 1997-12-09 | Lynx Therapeutics, Inc. | Massively parallel sequencing of sorted polynucleotides |
| WO1996038726A1 (en) | 1995-05-30 | 1996-12-05 | Ecole Polytechnique Federale De Lausanne (Epfl) | Covalently immobilized phospholipid bilayers on solid surfaces |
| US5780613A (en) | 1995-08-01 | 1998-07-14 | Northwestern University | Covalent lock for self-assembled oligonucleotide constructs |
| DE19646372C1 (de) | 1995-11-11 | 1997-06-19 | Evotec Biosystems Gmbh | Genotyp und Phänotyp koppelnde Verbindung |
| US5962228A (en) | 1995-11-17 | 1999-10-05 | Lynx Therapeutics, Inc. | DNA extension and analysis with rolling primers |
| US5763175A (en) | 1995-11-17 | 1998-06-09 | Lynx Therapeutics, Inc. | Simultaneous sequencing of tagged polynucleotides |
| US5780231A (en) | 1995-11-17 | 1998-07-14 | Lynx Therapeutics, Inc. | DNA extension and analysis with rolling primers |
| US6537776B1 (en) | 1999-06-14 | 2003-03-25 | Diversa Corporation | Synthetic ligation reassembly in directed evolution |
| US5846839A (en) | 1995-12-22 | 1998-12-08 | Glaxo Group Limited | Methods for hard-tagging an encoded synthetic library |
| US6027890A (en) | 1996-01-23 | 2000-02-22 | Rapigene, Inc. | Methods and compositions for enhancing sensitivity in the analysis of biological-based assays |
| US5898031A (en) | 1996-06-06 | 1999-04-27 | Isis Pharmaceuticals, Inc. | Oligoribonucleotides for cleaving RNA |
| DE19642751A1 (de) | 1996-10-16 | 1998-04-23 | Deutsches Krebsforsch | Saccharid-Bibliothek |
| PT971946E (pt) | 1997-01-21 | 2006-11-30 | Gen Hospital Corp | Selecção de proteínas utilizando fusões arn-proteína |
| WO2002034935A2 (en) | 2000-10-27 | 2002-05-02 | Research Development Foundation | In vitro selection of signaling aptamers |
| US5888737A (en) | 1997-04-15 | 1999-03-30 | Lynx Therapeutics, Inc. | Adaptor-based sequence analysis |
| US6969488B2 (en) | 1998-05-22 | 2005-11-29 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
| US20020034732A1 (en) | 1997-07-30 | 2002-03-21 | Daniel J. Capon | Compositions and methods for determining anti-viral drug susceptibility and resistance and anti-viral drug screening |
| WO1999010485A1 (en) | 1997-08-29 | 1999-03-04 | Selective Genetics, Inc. | Methods using phage display for selecting internalizing ligands for gene delivery |
| US6607878B2 (en) | 1997-10-06 | 2003-08-19 | Stratagene | Collections of uniquely tagged molecules |
| EP1090137B1 (de) * | 1998-06-22 | 2002-04-03 | Larova Biochemie GmbH | Herstellung von polymeren aus nukleotidischen und/oder nicht-nukleotidischen bausteinen auf enzymatischem weg |
| US6846655B1 (en) | 1998-06-29 | 2005-01-25 | Phylos, Inc. | Methods for generating highly diverse libraries |
| AU6502599A (en) | 1998-10-05 | 2000-04-26 | Lynx Therapeutics, Inc. | Enzymatic synthesis of oligonucleotide tags |
| CA2346989A1 (en) | 1998-10-19 | 2000-04-27 | The Board Of Trustees Of The Leland Stanford Junior University | Dna-templated combinatorial library chemistry |
| US5942609A (en) | 1998-11-12 | 1999-08-24 | The Porkin-Elmer Corporation | Ligation assembly and detection of polynucleotides on solid-support |
| ES2280131T3 (es) | 1998-12-02 | 2007-09-01 | Adnexus Therapeutics, Inc. | Fusiones de adn-proteina y utilizaciones de las mismas. |
| US6087112A (en) | 1998-12-30 | 2000-07-11 | Oligos Etc. Inc. | Arrays with modified oligonucleotide and polynucleotide compositions |
| US7033753B1 (en) | 1999-01-15 | 2006-04-25 | University Of Rochester | Compositions and methods for nonenzymatic ligation of oligonucleotides and detection of genetic polymorphisms |
| AU2951599A (en) | 1999-04-08 | 2000-11-14 | Pavel Sergeev | Synthesis of biologically active compounds in cells |
| ATE347616T1 (de) * | 1999-04-30 | 2006-12-15 | Cyclops Genome Sciences Ltd | Ribonukleinsäurederivate |
| US7270969B2 (en) | 1999-05-05 | 2007-09-18 | Phylogica Limited | Methods of constructing and screening diverse expression libraries |
| JP4803933B2 (ja) | 1999-08-27 | 2011-10-26 | ブリストル−マイヤーズ スクウィブ カンパニー | インビトロ翻訳タンパク質の符号化方法および選別方法 |
| AU7703400A (en) | 1999-09-14 | 2001-04-17 | Xenoport, Inc. | Substrates and screening methods for transport proteins |
| EP1218544B1 (en) | 1999-10-04 | 2009-06-03 | The University of Medicine and Dentistry of New Jersey | TAR RNA binding peptides |
| US6844324B1 (en) | 1999-11-12 | 2005-01-18 | Massachusetts Institute Of Technology | Modular peptide mediated intracellular delivery system and uses therefore |
| AU2001241668A1 (en) | 2000-02-23 | 2001-09-03 | Xenoport, Inc. | Self-encoded combinatorial synthesis of compound multiplets |
| US6936467B2 (en) * | 2000-03-27 | 2005-08-30 | University Of Delaware | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides |
| US7998673B2 (en) | 2000-03-29 | 2011-08-16 | Lgc Limited | Hybridisation beacon and method of rapid sequence detection and discrimination |
| US6479262B1 (en) * | 2000-05-16 | 2002-11-12 | Hercules, Incorporated | Solid phase enzymatic assembly of polynucleotides |
| US6994963B1 (en) | 2000-07-10 | 2006-02-07 | Ambion, Inc. | Methods for recombinatorial nucleic acid synthesis |
| US20020072887A1 (en) | 2000-08-18 | 2002-06-13 | Sandor Szalma | Interaction fingerprint annotations from protein structure models |
| US6627748B1 (en) | 2000-09-11 | 2003-09-30 | The Trustees Of Columbia University In The City Of New York | Combinatorial fluorescence energy transfer tags and their applications for multiplex genetic analyses |
| EP1331572B1 (en) | 2000-09-20 | 2012-08-08 | ARKRAY, Inc. | Client support system |
| JP2002315577A (ja) | 2000-11-14 | 2002-10-29 | Gencom Co | 核酸ライブラリーの作製方法 |
| US20030049616A1 (en) | 2001-01-08 | 2003-03-13 | Sydney Brenner | Enzymatic synthesis of oligonucleotide tags |
| JP4128453B2 (ja) | 2001-03-19 | 2008-07-30 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | 新規分子機能の進化 |
| JP2004535193A (ja) | 2001-06-20 | 2004-11-25 | ヌエヴォリューション・アクティーゼルスカブ | 鋳型化された分子およびかかる分子の使用方法 |
| US20030143561A1 (en) | 2001-06-20 | 2003-07-31 | Nuevolution A/S | Nucleoside derivatives for library preparation |
| EP1401850A1 (en) | 2001-06-20 | 2004-03-31 | Nuevolution A/S | Nucleoside derivatives for library preparation |
| US20060234231A1 (en) | 2001-06-20 | 2006-10-19 | Nuevolution A/S | Microarrays displaying encoded molecules |
| US20070213519A1 (en) | 2002-03-01 | 2007-09-13 | Nuevolution A/S | Building Block Forming A C=C Double Bond Upon Reaction |
| KR100916889B1 (ko) | 2002-03-08 | 2009-09-09 | 아이드게노쉬쉐 테흐니쉐 호흐슐레 쥬리히 | 암호화된 자가-조립 화학적 라이브러리(ｅｓａｃｈｅｌ) |
| CN101006177B (zh) | 2002-03-15 | 2011-10-12 | 纽韦卢森公司 | 改善的用于合成模制分子的方法 |
| WO2003078446A2 (en) | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block forming a c-c or a c-hetero atom bond upon reaction |
| EP1490384A2 (en) | 2002-03-15 | 2004-12-29 | Nuevolution A/S | A building block forming a c-c bond upon reaction |
| WO2003078626A2 (en) | 2002-03-15 | 2003-09-25 | Nuevolution A/S | A building block capable of transferring a functional entity |
| AU2003240436A1 (en) | 2002-06-20 | 2004-01-06 | Nuevolution A/S | Microarrays displaying encoded molecules |
| JP2006510348A (ja) | 2002-07-18 | 2006-03-30 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・レランド・スタンフォード・ジュニア・ユニバーシティ | 蛍光消光脱離基を用いる化学ライゲーションの検出 |
| EP1527173A1 (en) | 2002-07-23 | 2005-05-04 | Nuevolution A/S | Gene shuffing by template switching |
| AU2003247266A1 (en) | 2002-08-01 | 2004-02-23 | Nuevolution A/S | Multi-step synthesis of templated molecules |
| WO2004016767A2 (en) | 2002-08-19 | 2004-02-26 | The President And Fellows Of Harvard College | Evolving new molecular function |
| EP1539953A2 (en) | 2002-09-12 | 2005-06-15 | Nuevolution A/S | Proximity-aided synthesis of templated molecules |
| CN106337046B (zh) | 2002-10-30 | 2021-03-23 | 纽韦卢森公司 | 合成双功能复合物的方法 |
| ATE450609T1 (de) | 2002-12-19 | 2009-12-15 | Nuevolution As | Durch quasizufallsstrukturen und funktionen geführte synthesemethode |
| WO2004074501A2 (en) | 2003-02-21 | 2004-09-02 | Nuevolution A/S | A method for obtaining structural information about an encoded molecule |
| US20070026397A1 (en) | 2003-02-21 | 2007-02-01 | Nuevolution A/S | Method for producing second-generation library |
| US7915201B2 (en) | 2003-03-20 | 2011-03-29 | Nuevolution A/S | Ligational encoding of small molecules |
| WO2005008240A2 (en) | 2003-07-03 | 2005-01-27 | Biogen Idec Ma Inc. | STRUCTURAL INTERACTION FINGERPRINT (SIFt) |
| AU2004257200A1 (en) | 2003-07-07 | 2005-01-27 | Cellay Llc | Hairpin-labeled probes and methods of use |
| EP1533385A1 (en) | 2003-09-05 | 2005-05-25 | Nuevolution A/S | Templated compounds for generation of encoded molecules and directional methods using such compounds |
| WO2005026686A2 (en) | 2003-09-09 | 2005-03-24 | Compass Genetics, Llc | Multiplexed analytical platform |
| ATE447626T1 (de) | 2003-09-18 | 2009-11-15 | Nuevolution As | Methode zur gewinnung struktureller informationen kodierter moleküle und zur selektion von verbindungen |
| WO2005050224A2 (en) | 2003-11-13 | 2005-06-02 | Epitome Biosystems Inc. | Small molecule and peptide arrays and uses thereof |
| JP5646127B2 (ja) | 2003-12-17 | 2014-12-24 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーＧｌａｘｏＳｍｉｔｈＫｌｉｎｅ ＬＬＣ | コードされたライブラリーの合成のための方法 |
| US7972994B2 (en) | 2003-12-17 | 2011-07-05 | Glaxosmithkline Llc | Methods for synthesis of encoded libraries |
| US20050153321A1 (en) | 2003-12-30 | 2005-07-14 | Saba James A. | Libraries of multiple-ligand-conjugated nucleic acids |
| EP1713936B1 (en) | 2004-02-12 | 2009-12-09 | Population Genetics Technologies Ltd Corporation of Great Britain | Genetic analysis by sequence-specific sorting |
| US20090239211A1 (en) | 2004-02-17 | 2009-09-24 | Nuevolution A/S | Method For Enrichment Involving Elimination By Mismatch Hybridisation |
| DE602005017370D1 (de) | 2004-03-22 | 2009-12-10 | Nuevolution As | Ligationscodierung unter verwendung von oligonukleotidbausteinen |
| US7405287B2 (en) | 2004-08-03 | 2008-07-29 | Board Of Regents, The University Of Texas System | Method of treating a cancer |
| US7745614B2 (en) | 2004-09-03 | 2010-06-29 | The Board Of Trustees Of The Leland Stanford Junior University | Universal linker compositions for the release or transfer of chemical agents from a polynucleotide |
| WO2006047791A2 (en) | 2004-10-27 | 2006-05-04 | The Board Of Trustees Of The Leland Stanford Junior University | Dna-templated combinatorial library device and method for use |
| AU2005300886B2 (en) | 2004-11-08 | 2009-11-12 | Vipergen Aps | Structural nucleic acid guided chemical synthesis |
| US8168381B2 (en) | 2004-11-22 | 2012-05-01 | Peter Birk Rasmussen | Template directed split and mix systhesis of small molecule libraries |
| WO2006066003A2 (en) | 2004-12-17 | 2006-06-22 | Dynavax Technologies Corporation | Methods and compositions for induction or promotion of immune tolerance |
| CN101090979A (zh) * | 2004-12-22 | 2007-12-19 | 埃克斯魁恩公司 | 用于分析核酸混合物的探针、文库和试剂盒及其构建方法 |
| EP1856256B1 (en) * | 2005-01-21 | 2009-07-15 | President And Fellows Of Harvard College | Free reactant use in nucleic acid-templated synthesis |
| US7393665B2 (en) | 2005-02-10 | 2008-07-01 | Population Genetics Technologies Ltd | Methods and compositions for tagging and identifying polynucleotides |
| US7407757B2 (en) | 2005-02-10 | 2008-08-05 | Population Genetics Technologies | Genetic analysis by sequence-specific sorting |
| US20060211030A1 (en) | 2005-03-16 | 2006-09-21 | Sydney Brenner | Methods and compositions for assay readouts on multiple analytical platforms |
| CA2611512C (en) | 2005-06-09 | 2018-05-22 | Praecis Pharmaceuticals, Inc. | Methods for synthesis of encoded libraries |
| WO2006138560A2 (en) | 2005-06-17 | 2006-12-28 | President And Fellows Of Harvard College | Nucleic acid-templated chemistry in organic solvents |
| CA2616404A1 (en) | 2005-07-26 | 2007-02-01 | Oregon Health & Science University | Nanoparticle probes for capture, sorting and placement of targets |
| WO2007016488A2 (en) | 2005-07-29 | 2007-02-08 | Ensemble Discovery Corporation | Analysis of encoded chemical libraries |
| CN101321877B (zh) | 2005-10-03 | 2013-04-10 | 应用生物系统有限责任公司 | 用于扩增核酸的组合物、方法和试剂盒 |
| CA2626325A1 (en) | 2005-10-28 | 2007-05-10 | Praecis Pharmaceuticals Incorporated | Methods for identifying compounds of interest using encoded libraries |
| LT3018206T (lt) | 2005-12-01 | 2021-12-10 | Nuevolution A/S | Fermentiniai kodavimo būdai, skirti didelių bibliotekų efektyviai sintezei |
| US7537897B2 (en) | 2006-01-23 | 2009-05-26 | Population Genetics Technologies, Ltd. | Molecular counting |
| US7928211B2 (en) | 2006-05-03 | 2011-04-19 | Vipergen Pharmaceuticals Aps | Method for preparing compounds by nucleic acid directed synthesis |
| CN101528673B (zh) | 2006-10-26 | 2012-08-01 | 住友化学株式会社 | 不对称铜络合物结晶的制造方法 |
| CN101219219B (zh) | 2007-01-10 | 2013-02-13 | 北京普罗吉生物科技发展有限公司 | 包含血管抑素或其片段的复合物、其制备方法及应用 |
| ES2395240T3 (es) | 2007-10-22 | 2013-02-11 | Lgc Limited | Oligonucleótidos y usos de los mismos |
| JP4940311B2 (ja) | 2007-11-19 | 2012-05-30 | 国立大学法人北陸先端科学技術大学院大学 | 光クロスリンク能を有する光応答性人工ヌクレオチド |
| WO2009077173A2 (en) * | 2007-12-19 | 2009-06-25 | Philochem Ag | Dna-encoded chemical libraries |
| US20120107840A1 (en) | 2008-04-09 | 2012-05-03 | Sru Biosystems, Inc | Methods for Label Free Testing of Cells |
| JP4814904B2 (ja) | 2008-04-16 | 2011-11-16 | 国立大学法人北陸先端科学技術大学院大学 | 核酸類の配列選択的な精製方法 |
| JP5774474B2 (ja) * | 2008-05-02 | 2015-09-09 | エピセンター テクノロジーズ コーポレーションＥｐｉｃｅｎｔｒｅ Ｔｅｃｈｎｏｌｏｇｉｅｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｒｎａへの選択的な５’ライゲーションによるタグの付加 |
| TW201011006A (en) | 2008-06-16 | 2010-03-16 | Nuevolution As | IAP binding compounds |
| KR20110036638A (ko) | 2008-07-25 | 2011-04-07 | 리차드 더블유. 와그너 | 단백질 스크리닝 방법 |
| CA2750874A1 (en) | 2009-01-30 | 2010-08-05 | Oxford Nanopore Technologies Limited | Hybridization linkers |
| WO2010094036A1 (en) | 2009-02-13 | 2010-08-19 | X-Chem, Inc. | Methods of creating and screening dna-encoded libraries |
| WO2010094027A1 (en) | 2009-02-13 | 2010-08-19 | X-Body, Inc. | Identification of nucleic acid delivery vehicles using dna display |
| AU2010213510B2 (en) | 2009-02-16 | 2014-05-01 | Epicentre Technologies Corporation | Template-independent ligation of single-stranded DNA |
| WO2011005762A1 (en) | 2009-07-06 | 2011-01-13 | Trilink Biotechnologies | Chemically modified ligase cofactors, donors and acceptors |
| US8574864B2 (en) * | 2009-11-05 | 2013-11-05 | Epicentre Technologies Corporation | Methods and kits for 3'-end-tagging of RNA |
| DE102009058769A1 (de) * | 2009-12-16 | 2011-06-22 | MagForce Nanotechnologies AG, 10589 | Temperaturabhängige Aktivierung von katalytischen Nukleinsäuren zur kontrollierten Wirkstofffreisetzung |
| EP2553151A4 (en) | 2010-03-26 | 2013-07-31 | X Body Inc | USE OF INDUCED PLURIPOTENTIAL CELLS AND OTHER CELLS FOR SCREENING COMPOSITE LIBRARIES |
| CA2832672A1 (en) | 2010-04-16 | 2011-10-20 | Nuevolution A/S | Bi-functional complexes and methods for making and using such complexes |
| ES2926988T3 (es) | 2011-03-15 | 2022-10-31 | X Body Inc | Métodos de cribado de anticuerpos |
| US8846883B2 (en) | 2011-08-16 | 2014-09-30 | University Of Southhampton | Oligonucleotide ligation |
| SG10201605812YA (en) | 2011-09-07 | 2016-09-29 | Chem Inc X | Methods for tagging dna-encoded libraries |
| KR102146721B1 (ko) | 2012-07-13 | 2020-08-21 | 엑스-켐, 인크. | 폴리머라제에 의해 판독가능하지 않은 코딩 올리고뉴클레오티드 연결을 갖는 dna-코딩된 라이브러리 |
| GB201322692D0 (en) | 2013-12-20 | 2014-02-05 | Philochem Ag | Production of encoded chemical libraries |
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