EP0904540A1 - Methoden für die synthese von räumlich verteilten kombinatorischen bibliotheken mit festgelegten positionen - Google Patents

Methoden für die synthese von räumlich verteilten kombinatorischen bibliotheken mit festgelegten positionen

Info

Publication number
EP0904540A1
EP0904540A1 EP97916869A EP97916869A EP0904540A1 EP 0904540 A1 EP0904540 A1 EP 0904540A1 EP 97916869 A EP97916869 A EP 97916869A EP 97916869 A EP97916869 A EP 97916869A EP 0904540 A1 EP0904540 A1 EP 0904540A1
Authority
EP
European Patent Office
Prior art keywords
series
arrays
solid supports
array
supports
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.)
Withdrawn
Application number
EP97916869A
Other languages
English (en)
French (fr)
Inventor
Edmund J. Moran
John F. Cargill
Romaine R. Maiefski
Thomas J. Baiga
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ontogen Corp
Original Assignee
Ontogen Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ontogen Corp filed Critical Ontogen Corp
Publication of EP0904540A1 publication Critical patent/EP0904540A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/047—Simultaneous synthesis of different peptide species; Peptide libraries
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00452—Means for the recovery of reactants or products
    • B01J2219/00454—Means for the recovery of reactants or products by chemical cleavage from the solid support
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00457—Dispensing or evacuation of the solid phase support
    • B01J2219/0047—Pins
    • B01J2219/00472—Replaceable crowns
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/0054—Means for coding or tagging the apparatus or the reagents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00585—Parallel processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/0059—Sequential processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00592—Split-and-pool, mix-and-divide processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00718—Type of compounds synthesised
    • B01J2219/0072—Organic compounds
    • B01J2219/00725—Peptides
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/04—Libraries containing only organic compounds
    • C40B40/10—Libraries containing peptides or polypeptides, or derivatives thereof
    • 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
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B70/00—Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Definitions

  • solid support-based chemistry it is common in the practice to employ solid support-based chemistry for these methods.
  • a collection of solid supports are split into individual pools. These pools are then exposed to a series of reactive monomers, followed by a recombination step, in which the position of all solid supports is randomized.
  • the solid supports are then split into a new set of individual pools, exposed to a new series of reactive monomers, followed by a second recombination step. By repeating this split, react and recombine process all possible combinations of oligomers or compounds from the series of monomers employed are obtained, providing a large excess of solid supports are utilized.
  • the first, second and third rows of supports from the second and third arrays in the second series are redistributed to the third series of arrays for chemical transformation step #3 in a similar fashion.
  • the redistribution of supports between the chemical transformation steps # 1 and #2 and between steps #2 and #3 is functionally identical if one simply reorients the arrays such that rows become columns and columns become rows (such as accomplished by a 90 degree rotation). If such a reorientation of the second series of arrays occurs then the columns from the second series of arrays are redistributed to columns in the third series of arrays. Following this second redistribution, chemical transformation step #3 is carried out on the supports.
  • Step 10 The crown holders are positioned such that the crowns fit mto the wells of eight 96 2 mL-well polypropylene microtiter plates (available from Beckman Corp , Brea, CA), marked Plate 1, 2, 3, through 8 such that holder S3.1 is positioned with Plate 1, holder S3 2 is positioned with Plate 2, etc
  • the onentation is such that the columns (and therefore the rows) of the holders are aligned with the columns (and therefore the rows) of the plates
  • the dimensions of an array coverage in a plate would be from Rows A through H and from Columns 1 through 8 using the nomenclature common to the microtiter plate format
  • the crowns are treated with 5% tnfluoroacetic acid in dichloromethane for 30 m.
  • the crown holders are removed and the volatile contents of the microtiter plates evaporated under reduced pressure (20 mmHg)
  • the methods described in the body of the invention may be used to produce non-peptide, low molecular weight organic compound libraries.
  • the synthetic chemistry protocols are more complex in the syntheses of many of these compounds than those utilized to construct peptide libraries. Additionally, there are no general methods available to directly sequence the structure of most of these compounds. Thus, the ease by which a library is de-coded using the method described herein renders it suitable for the svnthesis of low molecular weight compounds.
  • the synthesis of a heterocyclic library is demonstrated. The synthesis of 1,4- benzodiazapin-2-ones follows the procedure of Ellman et. al. 17 and is shown in the accompanying schematic.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Steroid Compounds (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
EP97916869A 1996-03-22 1997-03-21 Methoden für die synthese von räumlich verteilten kombinatorischen bibliotheken mit festgelegten positionen Withdrawn EP0904540A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US1389796P 1996-03-22 1996-03-22
US13897P 1996-03-22
PCT/US1997/004500 WO1997035198A1 (en) 1996-03-22 1997-03-21 Methods for spatially-dispersed positionally-encoded combinatorial library synthesis

Publications (1)

Publication Number Publication Date
EP0904540A1 true EP0904540A1 (de) 1999-03-31

Family

ID=21762395

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97916869A Withdrawn EP0904540A1 (de) 1996-03-22 1997-03-21 Methoden für die synthese von räumlich verteilten kombinatorischen bibliotheken mit festgelegten positionen

Country Status (5)

Country Link
EP (1) EP0904540A1 (de)
JP (1) JP2001519763A (de)
AU (1) AU2537397A (de)
CA (1) CA2249419A1 (de)
WO (1) WO1997035198A1 (de)

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US5925562A (en) * 1995-04-25 1999-07-20 Irori Remotely programmable matrices with memories
US6284459B1 (en) 1995-04-25 2001-09-04 Discovery Partners International Solid support matrices with memories and combinatorial libraries therefrom
CN1181720A (zh) 1995-04-25 1998-05-13 伊萝莉公司 可远程编程的存储器材料及其应用
US6100026A (en) * 1995-04-25 2000-08-08 Irori Matrices with memories and uses thereof
US5961923A (en) * 1995-04-25 1999-10-05 Irori Matrices with memories and uses thereof
US6362009B1 (en) 1997-11-21 2002-03-26 Merck & Co., Inc. Solid phase synthesis of heterocycles
HUP0103260A3 (en) * 1998-03-23 2002-03-28 Harvard College Peptidomimetic compounds and process for their synthesis
US6541211B1 (en) * 1998-05-20 2003-04-01 Selectide Corporation Apparatus and method for synthesizing combinational libraries
US6858423B1 (en) 1998-06-05 2005-02-22 The Regents Of The University Of California Optical Amplification of molecular interactions using liquid crystals
US6284197B1 (en) 1998-06-05 2001-09-04 The Regents Of The University Of California Optical amplification of molecular interactions using liquid crystals
US7479472B1 (en) 1998-10-19 2009-01-20 The Board Of Trustees Of The Leland Stanford Junior University DNA-templated combinatorial library chemistry
SE9902479D0 (sv) * 1999-06-30 1999-06-30 Amersham Pharm Biotech Ab Particle classification as marker
AU1075701A (en) 1999-10-08 2001-04-23 Protogene Laboratories, Inc. Method and apparatus for performing large numbers of reactions using array assembly
US6799120B2 (en) * 2000-02-03 2004-09-28 Nanoscale Combinatorial Synthesis, Inc. Nonredundant split/pool synthesis of combinatorial libraries
US7129326B2 (en) 2000-04-14 2006-10-31 Genencor International, Inc. Methods for selective targeting
EP1360500B1 (de) 2000-04-14 2010-01-13 Genencor International, Inc. Verfahren zur selektiven zielen
US7727713B2 (en) 2001-06-20 2010-06-01 Nuevolution A/S Templated molecules and methods for using such molecules
US7842498B2 (en) 2001-11-08 2010-11-30 Bio-Rad Laboratories, Inc. Hydrophobic surface chip
DE60324778D1 (de) 2002-03-15 2009-01-02 Nuevolution As Eine verbesserte methode zur synthese von matritzenabhängigen molekülen
US10731151B2 (en) 2002-03-15 2020-08-04 Nuevolution A/S Method for synthesising templated molecules
AU2003247266A1 (en) 2002-08-01 2004-02-23 Nuevolution A/S Multi-step synthesis of templated molecules
WO2004038415A1 (en) * 2002-10-24 2004-05-06 Biacore Ab Assay with co-immobilized ligands
CN102838654B (zh) 2002-10-30 2016-05-18 纽韦卢森公司 合成双功能复合物的方法
DE60330406D1 (de) 2002-12-19 2010-01-14 Nuevolution As Durch quasizufallsstrukturen und funktionen geführte synthesemethode
US20070026397A1 (en) 2003-02-21 2007-02-01 Nuevolution A/S Method for producing second-generation library
US20040235056A1 (en) * 2003-05-07 2004-11-25 Mallouk Thomas E. Method of assembling particle libraries
ATE447626T1 (de) 2003-09-18 2009-11-15 Nuevolution As Methode zur gewinnung struktureller informationen kodierter moleküle und zur selektion von verbindungen
US7795007B2 (en) 2003-09-23 2010-09-14 Wisconsin Alumni Research Foundation Detection of post-translationally modified peptides with liquid crystals
JP4668911B2 (ja) 2003-09-23 2011-04-13 ウィスコンシン アルムニ リサーチ ファンデイション アフィニティー・マイクロコンタクトプリントされた生体分子を検出するための液晶の使用
US7341872B1 (en) 2004-04-29 2008-03-11 Uop Llc Multiautoclave with set of vessels for combinatorial synthesis of zeolites and other materials
LT3018206T (lt) 2005-12-01 2021-12-10 Nuevolution A/S Fermentiniai kodavimo būdai, skirti didelių bibliotekų efektyviai sintezei
SI2558577T1 (sl) 2010-04-16 2019-05-31 Nuevolution A/S Bifunkcionalni kompleksi in metode za pripravo in uporabo takšnih kompleksov

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Also Published As

Publication number Publication date
WO1997035198A1 (en) 1997-09-25
CA2249419A1 (en) 1997-09-25
AU2537397A (en) 1997-10-10
JP2001519763A (ja) 2001-10-23

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