Hairless protein-interacting partner complexes and methods thereto

• US 20040086945A1
• Filed: 06/02/2003
• Published: 05/06/2004
• Est. Priority Date: 06/03/2002
• Status: Abandoned Application

• Current Assignee: The Procter & Gamble Company
• Original Assignee: The Procter & Gamble Company
• Inventors: Gerwe, Gina Sue, Toerner, Daniel Robert, Sreekrishna, Kotikanyadanam
• Application Number:
  US10/452,858
• Publication Number:
  US 20040086945A1
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: A61K 2800/78 Enzyme modulators, e.g. Enzyme agonists
• CPC Class Codes: A61K 2800/782 Enzyme inhibitors; Enzyme antagonists
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/16 Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 38/51 Lyases (4)
• CPC Class Codes: A61K 8/36 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 8/44 Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
• CPC Class Codes: A61Q 7/00 Preparations for affecting hair growth
• CPC Class Codes: A61Q 7/02 Preparations for inhibiting or slowing hair growth
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

The present invention relates to complexes of hairless protein and proteins or nucleic acids identified as interacting with hairless protein using a yeast two-hybrid assay system. Hairless protein is indispensable for mammalian hair growth. Therefore, such interacting complexes are useful for screening test compounds for inhibition or enhancement of hair growth.

Claims

1. A composition comprising a mouse Hrt protein-human interacting partner protein complex wherein the human interacting partner protein comprises a molecule selected from the group consisting of ubiquitous receptor UR, SEQ ID NO:

4, MAP1A, SEQ ID NO;

8, KIAA0930 protein, SEQ ID NO;

13, and monocyte antigen CD14.

8. A method of assaying a test compound for agonist or antagonist activity for the composition of claim 1, comprising:

a) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the absence of the test compound;

b) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the presence of the test compound;

wherein when the level measured in step b) is greater than the level in step a), the test compound has agonist activity, and wherein when the level measured in step b) is less than the level in step a), the test compound has antagonist activity.

15. A method of inhibiting hair growth on a surface in a subject in need thereof, comprising applying to the surface a growth-inhibiting amount of a compound having antagonist activity for the composition of claim 1 for a time sufficient to inhibit hair growth on the surface.

16. A method of increasing hair growth on a surface in a subject in need thereof, comprising applying to the surface a growth-increasing amount of a compound having agonist activity for the composition of claim 1 for a time sufficient to increase hair growth on the surface.

2. A composition comprising a mouse Hrt protein-human interacting partner protein complex wherein the human interacting partner protein is encoded by a nucleic acid comprising SEQ ID NO:

11, SEQ ID NO;

90, or SEQ ID NO;

99.

9. A method of assaying a test compound for agonist or antagonist activity for the composition of claim 2, comprising:

a) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the absence of the test compound;

b) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the presence of the test compound;

wherein when the level measured in step b) is greater than the level in step a), the test compound has agonist activity, and wherein when the level measured in step b) is less than the level in step a), the test compound has antagonist activity.

17. A method of inhibiting hair growth on a surface in a subject in need thereof, comprising applying to the surface a growth-inhibiting amount of a compound having antagonist activity for the composition of claim 2 for a time sufficient to inhibit hair growth on the surface.

18. A method of increasing hair growth on a surface in a subject in need thereof, comprising applying to the surface a growth-increasing amount of a compound having agonist activity for the composition of claim 2 for a time sufficient to increase hair growth on the surface.

3. A composition comprising a mouse Hrt protein-human interacting partner protein complex wherein the human interacting partner protein comprises a molecule selected from the group consisting of sphingolipid activator protein, beta-synuclein, C11 protein, vesicle-associated membrane protein 2, SEQ ID NO:

25, aldolase A, CGI-106 protein, hypothalamus protein HSMNP1, alpha enolase, SEQ ID NO;

35, POM-ZP3, SEQ ID NO;

39, quinone oxidoreductase, SEQ ID NO;

43, pumilio 1, VPS41, and KIAA0614 protein.

10. A method of assaying a test compound for agonist or antagonist activity for the composition of claim 3, comprising:

a) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the absence of the test compound;

b) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the presence of the test compound;

wherein when the level measured in step b) is greater than the level in step a), the test compound has agonist activity, and wherein when the level measured in step b) is less than the level in step a), the test compound has antagonist activity.

4. A composition comprising a mouse Hrt protein-human interacting partner nucleic acid complex wherein the human interacting partner nucleic acid comprises SEQ ID NO:

95.

11. A method of assaying a test compound for agonist or antagonist activity for the composition of claim 4, comprising:

a) measuring a level of interaction between mouse Hrt protein and the human interacting partner nucleic acid in the absence of the test compound;

b) measuring a level of interaction between mouse Hrt protein and the human interacting partner nucleic acid in the presence of the test compound;

wherein when the level measured in step b) is greater than the level in step a), the test compound has agonist activity, and wherein when the level measured in step b) is less than the level in step a), the test compound has antagonist activity.

5. A composition comprising a mouse Hrt protein-human interacting partner protein complex where the human interacting partner protein comprises a molecule selected from the group consisting of SEQ ID NO:

52, SEQ ID NO;

54, SEQ ID NO;

58, splicing factor CC1.4, SEQ ID NO;

65, SEQ ID NO;

67, ubiquitin, beta-mannosidase, SEQ ID NO;

85, and SEQ ID NO;

87.

12. A method of assaying a test compound for agonist or antagonist activity for the composition of claim 5, comprising:

a) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the absence of the test compound;

b) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the presence of the test compound;

wherein when the level measured in step b) is greater than the level in step a), the test compound has agonist activity, and wherein when the level measured in step b) is less than the level in step a), the test compound has antagonist activity.

6. A composition comprising a mouse Hrt protein-human interacting partner protein complex wherein the human interacting partner protein is encoded by a nucleic acid comprising

13. A method of assaying a test compound for agonist or antagonist activity for the composition of claim 6, comprising:

a) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the absence of the test compound;

b) measuring a level of interaction between mouse Hrt protein and the human interacting partner protein in the presence of the test compound;

wherein when the level measured in step b) is greater than the level in step a), the test compound has agonist activity, and wherein when the level measured in step b) is less than the level in step a), the test compound has antagonist activity.

7. A composition comprising a mouse Hrt protein-human interacting partner nucleic acid complex wherein the human interacting partner nucleic acid comprises SEQ ID NO:

92, SEQ ID NO;

94, SEQ ID NO;

96, or SEQ ID NO;

98.

14. A method of assaying a test compound for agonist or antagonist activity for the composition of claim 7, comprising:

a) measuring a level of interaction between mouse Hrt protein and the human interacting partner nucleic acid in the absence of the test compound;

b) measuring a level of interaction between mouse Hrt protein and the human interacting partner nucleic acid in the presence of the test compound;

wherein when the level measured in step b) is greater than the level in step a), the test compound has agonist activity, and wherein when the level measured in step b) is less than the level in step a), the test compound has antagonist activity.