Methods of synthesizing diverse collections of oligomers

• US 5,789,162 A
• Filed: 06/07/1995
• Issued: 08/04/1998
• Est. Priority Date: 09/18/1991
• Status: Expired due to Fees

• Current Assignee: Affymax Incorporated
• Original Assignee: Affymax Incorporated
• Inventors: Barrett, Ronald W., Gallop, Mark A., Dower, William J.
• Primary Examiner(s): Horlick, Kenneth R.
• Application Number:
  US08/484,505
• Time in Patent Office: 1,154 Days
• Field of Search: 435/6, 435/91.2, 435/91.1, 435/5, 435/7.1, 435/4, 435/18, 435/23, 435/24, 436/501, 436/518, 436/524, 436/528, 436/531, 436/86, 436/89, 436/90, 436/94, 530/350, 530/387.1, 530/333, 530/335, 530/334, 536/23.5, 536/25.3
• US Class Current: 506/28
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00306 Reactor vessels in a multiple arrangement
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/00466 in a slurry
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00502 Particles of irregular geometry
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00542 Alphanumeric characters
• CPC Class Codes: B01J 2219/00545 Colours
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00554 Physical means
• CPC Class Codes: B01J 2219/00563 Magnetic means
• CPC Class Codes: B01J 2219/00565 Electromagnetic means
• CPC Class Codes: B01J 2219/00572 Chemical means
• CPC Class Codes: B01J 2219/00574 radioactive
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00592 : Split-and-pool, mix-and-divide processes
• CPC Class Codes: B01J 2219/00596 : Solid-phase processes
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/0072 : Organic compounds
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00731 : Saccharides
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07H 19/10 : with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/14 : Pyrrolo-pyrimidine radicals
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: Y10S 435/81 : Packaged device or kit
• CPC Class Codes: Y10T 436/143333 : Saccharide [e.g., DNA, etc.]

Abstract

A general stochastic method for synthesizing random oligomers on particles is disclosed. A further aspect of the invention relates to the use of identification tags on the particles to facilitate identification of the sequence of the monomers in the oligomer.

Claims

1. A method of recording each step in a synthesis of a compound, said compound being produced by step-by-step assembly of building blocks, said method comprising the steps of:

(a) coupling to a solid support a first building block and a first identifier tag under conditions compatible with immobilization of the first building block and the first identifier tag, wherein said first identifier tag identifies the first building block and wherein said first identifier tag is a nucleotide or oligonucleotide;

(b) repeating step (a) until the desired compound is prepared on said solid support; and

(c) sequencing the identifier tags that are present on said solid support to identify the corresponding building blocks coupled to said solid support.

2. A method of claim 1 wherein said step of sequencing comprises hybridizing the identifier tags to a plurality of oligonucleotide probes.

3. The method of claim 2, wherein said first identifier tag is an oligonucleotide from 3 to 10 nucleotides in length.

4. The method of claim 2, wherein said first identifier tag is an oligonucleotide from 50 to 150 nucleotides in length.

5. The method of claim 2, wherein said first identifier tag is coupled to another identifier tag.

6. The method of claim 2, wherein said first identifier tag is activated to form a phosphoramidite group prior to its coupling to the solid support.