Capture compounds, collections thereof and methods for analyzing the proteome and complex compositions

• US 9,034,798 B2
• Filed: 02/26/2010
• Issued: 05/19/2015
• Est. Priority Date: 01/16/2003
• Status: Expired due to Fees

• Current Assignee: Caprotec Bioanalytics GmbH
• Original Assignee: Caprotec Bioanalytics GmbH
• Inventors: Little, Daniel Paul, Siddiqi, Suhaib Mahmood, Grealish, Matthew Peter, Marappan, Subramanian, Hassman, Chester Frederick III, Yip, Ping, Kster, Hubert
• Primary Examiner(s): Gross, Christopher M
• Application Number:
  US12/660,511
• Publication Number:
  US 20100248264A1
• Time in Patent Office: 1,908 Days
• Field of Search: None
• US Class Current: 506/13
• CPC Class Codes: C07C 2603/74 Adamantanes
• CPC Class Codes: C07C 69/76 Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 69/96 Esters of carbonic or haloformic acids
• CPC Class Codes: C07D 207/404 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
• CPC Class Codes: C07D 207/46 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 209/48 with oxygen atoms in positions 1 and 3, e.g. phthalimide
• CPC Class Codes: C07D 211/60 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 211/78 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 213/79 Acids; Esters
• CPC Class Codes: C07D 215/48 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 239/54 as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
• CPC Class Codes: C07D 239/545 with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
• CPC Class Codes: C07D 241/44 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 261/12 Oxygen atoms
• CPC Class Codes: C07D 271/07 with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 303/14 by free hydroxyl radicals
• CPC Class Codes: C07D 303/16 by esterified hydroxyl radicals
• CPC Class Codes: C07D 317/36 Alkylene carbonates; Substituted alkylene carbonates
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems
• CPC Class Codes: C07D 519/00 : Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
• CPC Class Codes: G01N 33/6803 : General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: G01N 33/6842 : Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
• CPC Class Codes: G01N 33/6845 : Methods of identifying protein-protein interactions in protein mixtures
• CPC Class Codes: G01N 33/6848 : Methods of protein analysis involving mass spectrometry

Abstract

Capture compounds and collections thereof and methods using the compounds for the analysis of biomolecules are provided. In particular, collections, compounds and methods are provided for analyzing complex protein mixtures, such as the proteome. The compounds are multifunctional reagents that provide for the separation and isolation of complex protein mixtures. Automated systems for performing the methods also are provided.

Claims

1. A method for assessing interactions of a molecule Y with targets and non-targets, comprising:

(a) selecting a molecule whose interactions with targets and non-targets are to be assessed, and providing one or more capture compound(s) that present(s) the molecule, wherein;

the capture compound has the formula;

2. The method of claim 1, wherein Q is biotin or an oligonucleotide.

3. The method of claim 1, wherein:

X is an azide; and

Q is biotin or an oligonucleotide.

4. The method of claim 3, wherein Y is an enzyme inhibitor.

5. The method of claim 1, wherein Y is an enzyme inhibitor.

6. The method of claim 1, wherein X is

7. The method of claim 4, wherein X is

8. The method of claim 1, wherein Q is an oligonucleotide.

9. The method of claim 1, wherein X an azide;

and Q is biotin.

10. The method of claim 9, wherein Z is selected from the group consisting of among serine, threonine, lysine, tyrosine and cysteine.

11. The method of claim 1, wherein the capture compound comprises a mass modifying tag linked to Z.

12. The method of claim 1, wherein the capture compounds further comprise a solubility group W that influences the solubility properties of the capture compound.

13. The method of claim 1, further comprising identifying or detecting a captured protein by mass spectrometry.

14. The method of claim 1, further comprising identifying a function of a captured protein.

15. The method of claim 1, wherein the cell lysate or tissue is contacted with a plurality of different capture compounds.

16. The method of claim 1, wherein a concentration of capture compound is varied in a plurality of different reactions.

17. The method of claim 13, wherein the mass spectrometry is selected from among matrix assisted laser desorption ionization (MALDI), continuous or pulsed electrospray (ES) ionization, ionspray, thermo spray and massive cluster impact mass spectrometry.

18. The method of claim 17, wherein the mass spectrometry analysis is linear time-of-flight (TOF), reflectron time-of-flight, single quadruple, multiple quadruple, single magnetic sector, multiple magnetic sector, Fourier transform, ion cyclotron resonance (ICR) or ion trap.

19. The method of claim 1, wherein:

redesigning the drug results in a second drug with fewer side-effects or an increased therapeutic index compared to the first drug.

20. The method of claim 6 or 7 wherein the arylazide is: