Beta-sheet mimetics and use thereof as inhibitors of biologically active peptides or proteins
OwnerMichael Kahninventor
Life of this patent
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Abstract
There are disclosed β-sheet mimetics and methods relating to the same for imparting or stabilizing the β-sheet structure of a peptide, protein or molecule. In one aspect, the β-sheet mimetics are covalently attached at the end or within the length of the peptide or protein. The β-sheet mimetics have utility as inhibitors of one or more of proteases, kinases, CAAX, peptides binding to SH2 domains and MHC-I and/or MHC-II presentation of peptides to T cell receptors in warm-blooded animals.
Claims4
A method for inhibiting a kinase in a warm-blooded animal, comprising administering to the animal an effective amount of a β-sheet mimetic having the structure:
- 203
- wherein R1, R2 and R3 are independently selected from amino acid side chain moieties and derivatives thereof;
- A is selected from —C(═O)—, —(CH2)1-4—, —C(═O)(CH2)1-3—, —(CH2)1-2O—and —(CH2)1-2S—;
- B is selected from N and CH;
- C is selected from —C(═O)—, —(CH2)1-3—, —O—, —S—, —O—(CH2)1-2— and —S(CH2)1-2—;
- Y and Z represent the remainder of the molecule;
- and any two adjacent CH groups of the bicyclic ring may form a double bond.
A method for CAAX inhibition in a warm-blooded animal, comprising administering to the animal an effective amount of a β-sheet mimetic having the structure:
- 204
- wherein R1, R2 and R3 are independently selected from amino acid side chain moieties and derivatives thereof;
- A is selected from —C(═O)—, —(CH2)1-4—, —C(═O)(CH2)1-3—, —(CH2)1-2O— and —(CH2)1-2S—;
- B is selected from N and CH;
- C is selected from —(═O)—, —(CH2)1-3—, —O—, —S—, —O—(CH2)1-2— and —S(CH2)1-2—;
- Y and Z represent:
- the remainder of the molecule;
- and any two adjacent CH groups of the bicyclic ring may form a double bond.
A method for inhibiting peptide binding to SH2 domains in a warm-blooded animal, comprising administering to the animal an effective amount of a β-sheet mimetic having the structure:
- 205
- wherein R1, R2 and R3 are independently selected from amino acid side chain moieties and derivatives thereof;
- A is selected from —C(═O)—, —(CH2)1-4—, —C(═O)(CH2)1-3—, —(CH2)1-2O— and —(CH2)1-2S—;
- B is selected from N and CH;
- C is selected from —C(═O)—, —(CH2)1-3—, —O—, —S—, —O—(CH2)1-2— and —S(CH2)1-2—;
- Y and Z represent the remainder of the molecule;
- and any two adjacent CH groups of the bicyclic ring may form a double bond.
A method for inhibiting MHC-I and/or MHC-II presentation of peptides to T cell receptors in a warm-blooded animal, comprising administering to the animal an effective amount of a β-sheet mimetic having the structure:
- 206
- wherein R1, R2 and R3 are independently selected from amino acid side chain moieties and derivatives thereof;
- A is selected from —C(═O)—, —(CH2)1-4—, —C(═O)(CH2)1-3—, —(CH2)1-2O—and —(CH2)1-2S—;
- B is selected from N and CH;
- C is selected from —(═O)—, —(CH2)1-3—, —O—, —S—, —O—(CH2)1-2— and —S(CH2)1-2—;
- Y and Z represent:
- the remainder of the molecule;
- and any two adjacent CH groups of the bicyclic ring may form a double bond.
Dependencies are inferred from the claim text.