Antibody-catalyzed deuteration, tritiation, dedeuteration or detritiation of carbonyl compounds

• US 6,440,710 B1
• Filed: 12/10/1998
• Issued: 08/27/2002
• Est. Priority Date: 12/10/1998
• Status: Expired due to Fees

• Current Assignee: The Scripps Research Institute
• Original Assignee: The Scripps Research Institute
• Inventors: Keinan, Ehud, Shulman, Avidor
• Primary Examiner(s): Naff, David M.
• Application Number:
  US09/208,381
• Time in Patent Office: 1,356 Days
• Field of Search: 435/147, 435/148, 435/188.5, 435/345, 435/346
• US Class Current: 435/148
• CPC Class Codes: C12P 13/02 Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes peptides C12P21/00 or C07K

Abstract

Methods are provided for deuteration, tritiation, dedeuteration or detritiation of a carbonyl compound. A catalytic antibody that catalyzes an aldol addition reaction is contacted with a carbonyl compound to exchange at least one hydrogen atom of the carbonyl compound with a deterium or tritium atom of an isotopically enriched water molecule, or to exchange at least one deuterium or tritium atom of the carbonyl compound with a hydrogen atom. The aldol addition reaction may be between an aliphatic ketone donor and an aldehyde acceptor. Isotopically enriched water molecules include deuterium hydrogen oxide, dideuterium oxide, tritium hydrogen oxide, ditritium oxide and deuterium tritium oxide. The catalytic antibody may be that secreted by hybridoma 38C2 (ATCC HB 12005) or 33F12 (ATCC HB 12004).

Claims

1. A method of deuterating or tritiating a carbonyl compound, the method comprising the steps of contacting the carbonyl compound with a catalytic antibody for catalyzing an aldol addition reaction in a presence of an aqueous solution enriched with an isotopically enriched water molecules, thereby exchanging at least one hydrogen atom in said carbonyl compound with a deuterium or tritium atom and obtaining a deuterated or tritiated carbonyl compound.

2. The method of claim 1, wherein said isotopically enriched water molecule is selected from the group consisting of deuterium hydrogen oxide, dideuterium oxide, tritium hydrogen oxide, ditritium oxide and deuterium tritium oxide.

3. The method of claim 1, wherein said catalytic antibody is capable of catalyzing said aldol addition reaction between an aliphatic ketone donor and an aldehyde acceptor.

4. The method of claim 1, wherein said catalytic antibody is characterized by having a lysine with an ε

-amino group in its binding pocket.

5. The method of claim 4, wherein said catalytic antibody is subject to inhibition with a molecule containing a β

-dicarbonyl group by formation of a complex between said β

-dicarbonyl group and the ε

-amino group of said lysine of said catalytic antibody.

6. The method of claim 5, wherein said complex is selected from the group consisting of a stable covalent vinylogous amide, a conjugated enamine and a Schiff base.

7. The method of claim 1 wherein said catalytic antibody controls the diastereofacial selectivity of said aldol addition reaction in both Cram-Felkin and anti-Cram-Felkin directions.

8. The method of claim 3, wherein said aliphatic ketone donor is selected from a group consisting of acetone, fluoroacetone, chloroacetone, 2-butanone, 3-pentanone, 2-pentanone, and dihydroxyacetone.

9. The method of claim 3, wherein said aldehyde acceptor is selected from a group represented by the following formulae:

10. The method of claim 1, wherein said catalytic antibody is secreted by hybridoma 38C2, having ATCC accession number HB 12005.

11. The method of claim 1, wherein said catalytic antibody is secreted by hybridoma 33F12, having ATCC accession number HB 12004.

12. The method of claim 1, wherein said catalytic antibody is elicited against a β

-dicarbonyl group containing hapten.

13. The method of claim 1, wherein said carbonyl compound is selected from the group consisting of molecules containing ketones and aldehydes.

14. The method of claim 1, wherein said carbonyl compound is selected from the group consisting of acetone, butanone, 2-heptanone, valeraldehyde, heptanal, decanal, ethyl 5-oxohexanoate, cyclopentanone, cyclohexanone and cycloheptanone.

15. A method of dedeuterating or detritiating a carbonyl compound, the method comprising the steps of contacting the carbonyl compound with a catalytic antibody for catalyzing an aldol addition reaction in a presence of an aqueous solution, thereby exchanging at least one deuterium or tritium atom in said carbonyl compound with a hydrogen atom and obtaining dedeuterated or detritiated carbonyl compound.