Method for determining mimotopes

• US 4,833,092 A
• Filed: 12/22/1986
• Issued: 05/23/1989
• Est. Priority Date: 04/22/1985
• Status: Expired due to Term

• Current Assignee: Coselco Mimotopes Pty Limited
• Original Assignee: Commonwealth Serum Laboratories Commission
• Inventors: Geysen, Hendrik M.
• Primary Examiner(s): Marantz, Sidney
• Application Number:
  US07/010,088
• Time in Patent Office: 883 Days
• Field of Search: 436/518, 436/543, 436/548, 436/501
• US Class Current: 436/501
• CPC Class Codes: G01N 33/53 Immunoassay; Biospecific binding assay; Materials therefor
• CPC Class Codes: G01N 33/6803 General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: G01N 33/6878 in eptitope analysis

Abstract

A method of detecting or determining the sequence of monomers which is a topographical equivalent of the ligand which is complementary to a particular receptor of interest, the method comprising the steps of:

1. synthesizing a plurality of catamers, each said catamer being of the general formula:

D.sub.2 --D.sub.1

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different to said first set of monomers; said plurality of catamers comprising catamers in which each designated monomer is systematically varied to contain members from the respective set of monomers;

2. contacting each catamer with the receptor of interest, and,

3. detecting or determining the presence or absence of binding between each catamer and said receptor.

Claims

1. A method of detecting or determining the sequence of monomers which is a topographical equivalent of the ligand which is complementary to a particular receptor of interest, the method comprising the steps of:

1. synthesizing a plurality of catamers, each said catamer being of the general formula;

space="preserve" listing-type="equation">D.sub.2 --D.sub.1

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers;

said plurality of catamers comprising catamers in which each designated monomer is systematically varied to contain members from the respective set of monomers;

2. contacting each catamer with the receptor of interest, and,

3. detecting or determining the presence or absence of binding between each catamer and said receptor.

2. A method according to claim 1, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

3. A method according to claim 1, wherein each of said plurality of catamers is synthesized on a solid support, and has the general formula:

space="preserve" listing-type="equation">Y--D.sub.2 --D.sub.1 --Lk--(solid support)

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers, Lk represents a linker molecule, and Y is a end group of the catamer.

4. A method according to claim 1, comprising the further step of systematically replacing the monomers in any of the catamers with their optical isomers, either individually or in combinations of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

5. A method according to claim 4, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

6. A method according to claim 1 comprising the further steps of:

A. synthesizing a plurality of additional catamers, each said additional catamer being of the general formula;

space="preserve" listing-type="equation">D.sub.2 --Sp--D.sub.1

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers, and Sp is a spacer molecule which can modify the relative orientation of the monomers D₁ and D₂ ;

B. contacting each said additional catamer with the receptor of interest, and,

C. detecting or determining the presence or absence of binding between each said additional catamer and said receptor.

7. A method according to claim 6, wherein each of said plurality of additional catamers is synthesized on a solid support, and has the general formula:

space="preserve" listing-type="equation">Y--D.sub.2 --Sp--D.sub.1 --Lk--(solid support)

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers, Sp is a spacer molecule which can modify the relative orientation of the monomers D₁ and D₂, Lk represents a linker molecule and Y is an end group of the catamer.

8. A method according to claim 6, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

9. A method according to claim 6, comprising the further step of systematically replacing the monomers in any of the catamers with their optical isomers, either individually or in combinations of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

10. A method according to claim 9, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

11. A method according to claim 1, comprising the further steps of:

a. synthesizing a further plurality of catamers, each said catamer being of the general formula;

space="preserve" listing-type="equation">D.sub.3 --D.sub.2 --D.sub.1,

space="preserve" listing-type="equation">or

space="preserve" listing-type="equation">D.sub.2 --D.sub.1 --D.sub.3

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers, and D₃ represents a designated monomer selected from a third set of monomers which may be the same as or different from either the first or the second set of monomers, and

b. contacting each said catamer with the receptor of interest, and,

c. detecting or determining the presence or absence of binding between each said catamer and said receptor.

12. A method according to claim 11, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

13. A method accordinag to claim 11, comprising the further step of systematically replacing the monomers in any of the catamers with their optical isomers, either individually or in combinations of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

14. A method according to claim 13, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

15. A method according to claim 11, wherein steps a., b. and c. are repeated with the systematic introduction of a spacer molecule, Sp, which can modify the relative orientation of the monomers D₁ and D₂, into all possible positions of the further pluralities of the catamers.

16. A method according to claim 15, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

17. A method according to claim 15, comprising the further step of systematically replacing the monomers in any of the catamers with their optical isomers, either individually or in combinations of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

18. A method according to claim 17, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

19. A method according to claim 11 comprising the further steps of:

A. synthesizing a plurality of additional catamers, each said additional catamer being of the general formula;

space="preserve" listing-type="equation">D.sub.2 --Sp--D.sub.1

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers, and Sp is a spacer molecule which can modify the relative orientation of the monomers D₁ and D₂ ;

B. contacting each said additional catamer with the receptor of interest, and,

C. detecting or determining the presence or absence of binding between each said additional catamer and said receptor.

20. A method according to claim 19, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

21. A method according to claim 19, wherein each of said plurality of additional catamers is synthesized on a solid support, and has the general formula:

space="preserve" listing-type="equation">Y--D.sub.2 --Sp--D.sub.1 --Lk--(solid support)

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers, Sp is a spacer molecule which can modify the relative orientation of the monomers D₁ and D₂, Lk represents a linker molecule and Y is an end group of the catamer.

22. A method according to claim 19, comprising the further step of systematically replacing the monomers in any of the catamers with their optical isomers, either individually or in combinations of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

23. A method according to claim 22, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

24. A method according to claim 11, wherein steps a., b. and c. are repeated with the systematic addition of further monomers to the catamers.

25. A method according to claim 24, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

26. A method according to claim 24, comprising the further step of systematically replacing the monomers in any of the catamers with their optical isomers, either individually or in combinations of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

27. A method according to claim 26, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

28. A method according to claim 24, wherein steps a., b. and c. are repeated with the systematic introduction of a spacer molecule, Sp, which can modify the relative orientation of the monomers D₁ and D₂, into all possible positions of the further pluralities of the catamers.

29. A method according to claim 28, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

30. A method according to claim 28, comprising the further step of systematically replacing the monomers in any of the catamers with their optical isomers, either individually or in combinations of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

31. A method according to claim 30, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

32. A method according to claim 24 comprising the further steps of:

A. synthesizing a plurality of additional catamers, each said additional catamer being of the general formula;

space="preserve" listing-type="equation">D.sub.2 --Sp--D.sub.1

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers, and Sp is a spacer molecule which can modify the relative orientation of the monomers D₁ and D₂ ;

B. contacting each said additional catamer with the receptor of interest, and,

C. detecting or determining the presence or absence of binding between each said additional catamer and said receptor.

33. A method according to claim 32, comprising the further step of systematically replacing the monomers in any of the catamers which bind with the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

34. A method according to claim 32, wherein each of said plurality of additional catamers is synthesized on a solid support, and has the general formula:

space="preserve" listing-type="equation">Y--D.sub.2 --Sp--D.sub.1 --Lk--(solid support)

wherein D₁ represents a designated monomer selected from a first set of monomers, and D₂ represents a designated monomer selected from a second set of monomers which may be the same as or different from said first set of monomers, Sp is a spacer molecule which can modify the relative orientation of the monomers D₁ and D₂, Lk represents a linker molecule and Y is an end group of the catamer.

35. A method according to claim 32, comprising the further step of systematically replacing the monomers in any of the catamers with their optical isomers, either individually or in combinations of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between each catamer and said receptor.

36. A method according to claim 35, comprising the further step of systematically replacing the monomers in any of the catamers which bind the receptor of interest, either individually or in combinations of monomers, with other monomers selected from the respective set(s) of monomers, and again performing the following steps:

contacting each catamer with the receptor of interest, and detecting or determining the presence or absence of binding between eact catamer and said receptor.