Photocleavable Protecting Groups

• US 20100324266A1
• Filed: 06/09/2010
• Published: 12/23/2010
• Est. Priority Date: 09/11/2000
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: McGall, Glenn H., Barone, Anthony D.
• Application Number:
  US12/797,559
• Publication Number:
  US 20100324266A1
• Time in Patent Office: Days
• US Class Current: 530/345
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 : with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 : Purine radicals
• CPC Class Codes: C07H 19/20 : with the saccharide radical esterified by phosphoric or polyphosphoric acids
• 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 1/04 : on carriers C07K1/003, C07K1/006 take precedence
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C07K 1/062 : for alpha- or omega-carboxy functions
• CPC Class Codes: C07K 1/063 : for alpha-amino functions
• CPC Class Codes: C07K 1/064 : for omega-amino or -guanidino functions
• CPC Class Codes: C07K 1/065 : for hydroxy functions, not being part of carboxy functions
• CPC Class Codes: C07K 1/066 : for omega-amido functions
• 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: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Novel compounds are provided, which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Y, wherein Y is a chemical structure as shown in FIG. 1. Also provided is a method of forming, from component molecules, a plurality of compounds on a support, each compound occupying a separate predefined region of the support, using the protected compounds described above.

Claims

1. A compound represented by the following structural formula:

Y-X

wherein;

X is a leaving group or a compound having a masked reactive site; and

Y is a photolabile protecting group selected from the group consisting of;

2. A method of attaching a molecule with a reactive site to a support comprising the steps of:

(a) providing a support with a reactive site;

(b) reacting the reactive site of a first compound of claim 1 with the support to form a bond; and

(c) removing the photolabile protecting group to provide a derivatized support comprising the compound of claim 1 with an unmasked reactive site immobilized thereon.

3. A method of forming, from component molecules, a plurality of support bound compounds, each compound occupying a separate predefined region of the support, said method comprising the steps of:

(a) activating a first predefined region of a support;

(b) binding a molecule to the first region, wherein said molecule is a compound of claim 1;

(c) repeating steps (a) and (b) on other predefined regions of the support whereby each of said other regions has bound thereto another molecule, wherein said another molecule is a compound of claim 1, and wherein said another molecules may be the same or different from that used in step (b);

(d) removing the photolabile protecting group from molecules bound to one of the regions of the support to provide a region bearing molecules with an unmasked reactive site;

(e) binding an additional molecule to the molecule with an unmasked reactive site, wherein the additional molecule is a compound of claim 1; and

(f) repeating steps (d) and (e) on regions of the support until a plurality of support bound compounds is formed from the component molecules, each compound occupying separate regions of the support.

4. A compound represented by the following structural formula:

Y-X

wherein;

X is a leaving group or a compound having a masked reactive site; and

Y is a photolabile protecting group bound to the leaving group or masking the masked reactive site, wherein Y is represented by the following structural formula;

5. The compound of claim 4, wherein X is a compound having a masked reactive site and X further comprises a reactive site.

6. The compound of claim 5, wherein X is a compound having a masked reactive site selected from the group consisting of an amino acid, a nucleoside, a nucleoside phosphoramidite, a nucleoside H-phosphonate, a nucleotide, a solid support, a peptide, an oligonucleotide, a protein, a hormone, an antibody, a polysaccharide, a monosacharide, a disaccharide, a solid support bound peptide, a solid support bound oligonucleotide, a solid support bound protein, a solid support bound hormone, a solid support bound antibody, a solid support bound polysaccharide, a solid support bound monosaccharide, or a solid support bound disaccharide.

7. The compound of claim 4, wherein Y is represented by the following structural formula:

8. The compound of claim 7, wherein the Y is represented by the following structural formula:

9. The compound of claim 8, wherein one of R₃ or R₄ is —

NO₂.

10. The compound of claim 7, wherein Y is selected from the group consisting of:

11. The compound of claim 4, wherein Y is a group represented by the following structural formula:

12. The compound of claim 11, wherein Y is represented by the following structural formula:

13. The compound of claim 12, wherein one of R₃ or R₉ is —

NO₂.

14. The compound of claim 11, wherein Y is represented by the following structural formula.

15. The compound of claim 14, wherein R₃, R₄, R₅ and R₆ are —

H and Q₃ is a dialkylamino.

16. The compound of claim 11, wherein Y is selected from the group consisting of:

18. A method of attaching a molecule with a reactive site to a support comprising the steps of:

(a) providing a support with a reactive site;

(b) reacting the reactive site of a first compound of claim 5 with the support to form a bond; and

(c) removing the photolabile protecting group to provide a derivatized support comprising the compound of claim 5 with an unmasked reactive site immobilized thereon.

19. A method of forming, from component molecules, a plurality of support bound compounds, each compound occupying a separate predefined region of the support, said method comprising the steps of:

(a) activating a region of the support;

(b) binding a molecule to the first region, wherein said molecule is a compound of claim 5;

(c) repeating steps (a) and (b) on other regions of the support whereby each of said other regions has bound thereto another molecule, wherein said another molecule is a compound of claim 5, and wherein said another molecules may be the same or different from that used in step (b);

(d) removing the photolabile protecting group from molecules bound to one of the regions of the support to provide a region bearing molecules with an unmasked reactive site;

(e) binding an additional molecule to the molecule with an unmasked reactive site, wherein the additional molecule is a compound of claim 5;

(f) repeating steps (d) and (e) on regions of the support until a plurality of support bound compounds is formed from the component molecules, each compound occupying separate regions of the support.

17. A compound represented by the following structural formula:

Y-X

wherein;

X is a leaving group or a compound having a masked reactive site; and

Y is a photolabile protecting group bound to the leaving group or masking the masked reactive site, wherein Y is represented by the following structural formula;

20. A method of attaching a molecule with a reactive site to a support comprising the steps of:

(a) providing a support with a reactive site;

(b) reacting the reactive site of a first compound of claim 17 with the support to form a bond; and

(c) removing the photolabile protecting group to provide a derivatized support comprising the compound of claim 17 with an unmasked reactive site immobilized thereon.

21. A method of forming, from component molecules, a plurality of support bound compounds, each compound occupying a separate predefined region of the support, said method comprising the steps of:

(a) activating a region of the support;

(b) binding a molecule to the first region, wherein said molecule is a compound of claim 17;

(c) repeating steps (a) and (b) on other regions of the support whereby each of said other regions has bound thereto another molecule, wherein said another molecule is a compound of claim 17, and wherein said another molecules may be the same or different from that used in step (b);

(d) removing the photolabile protecting group from molecules bound to one of the regions of the support to provide a region bearing molecules with an unmasked reactive site;

(e) binding an additional molecule to the molecule with an unmasked reactive site, wherein the additional molecule is a compound of claim 17;

(f) repeating steps (d) and (e) on regions of the support until a plurality of support bound compounds is formed from the component molecules, each compound occupying separate regions of the support.