Controlling protein levels in eucaryotic organisms

A compound for activating the ubiquitination of a target protein comprising;

• a) a ubiquitination recognition peptide element which is able to bind to either the E3 or E2 functional elements of the ubiquitination system, wherein said ubiquitination recognition peptide element has a molecular weight less than 30,000 and has a binding affinity for said E3 and/or E2 elements of the ubiquitination system of at least 102 M−1 and;
• b) a target protein binding element that is able to bind specifically to a target protein wherein said target protein binding element has a molecular weight of less than 30,000 and has a binding affinity for said target protein greater than
• wherein said ubiquitination recognition peptide element is covalently linked to said target protein binding element.

A compound for activating the ubiquitination of a target protein comprising;

• a) a ubiquitination recognition element which is able to bind to either the E3 or E2 functional elements of the ubiquitination system, wherein said ubiquitination recognition element has a molecular weight less than 30,000 and has a binding affinity for said E3 and/or E2 elements of the ubiquitination system of at least 102 M−1 and;
• b) a target protein binding peptide element that is able to bind specifically to a target protein wherein said target protein binding peptide element has a molecular weight of less than 30,000 and has a binding affinity for said target protein greater than 105 M−1,
• wherein said ubiquitination recognition element is covalently linked to said target protein binding peptide element.

A compound for activating the ubiquitination of a target protein comprising;

• a) a ubiquitination recognition peptide element which is able to bind to either the E3 or E2 elements of the ubiquitination system, wherein said ubiquitination recognition peptide element has a molecular weight less than 30,000 and has a binding affinity for said E3 and/or E2 elements of the ubiquitination system of at least 102 M−1 and;
• b) a target protein binding peptide element that is able to bind specifically to a target protein
• wherein said target protein binding peptide element has a molecular weight of less than 30,000 and has a binding affinity for said target protein greater than 105 M−1, wherein said ubiquitination recognition peptide element is covalently linked to said target protein binding peptide element.

A method of modulating the level and/or activity of at least one target protein in an eukaryotic cell via the modulation of ubiquitination of said at least one target protein comprising contacting said cell with a compound comprising;

• a) a ubiquitination recognition element which is able to bind to either the E3 or E2 elements of the ubiquitination system, wherein said ubiquitination recognition element has a molecular weight less than 30,000 and has a binding affinity for said E3 and/or E2 elements of the ubiquitination system of at least 102 M−1 and;
• b) a target protein binding element that is able to bind specifically to a target protein wherein said target protein binding element has a molecular weight of less than 30,000 and has a binding affinity for said target protein greater than 105 M−1,
• wherein said ubiquitination recognition element is covalently linked to said target protein binding element.

A method of treating an infection in a mammal comprising administering to said mammal an amount of a compound sufficient to eliminate and/or reduce said infection said compound comprising;

• a) a ubiquitination recognition element which is able to bind to either the E3 or E2 elements of the ubiquitination system, wherein said ubiquitination recognition element has a molecular weight less than 30,000 and has a binding affinity for said E3 and/or E2 elements of the ubiquitination system of at least 102 M−1 and;
• b) a target protein binding element that is able to bind specifically to a target protein wherein said target protein binding element has a molecular weight of less than 30,000 and has a binding affinity for said target protein greater than 105 M−1,
• wherein said ubiquitination recognition element is covalently linked to said target protein binding element.

A method of treating a tumor in a mammal comprising administering to said mammal an amount of a compound sufficient to reduce the size of said tumor, said compound comprising;

• a) a ubiquitination recognition element which is able to bind to either the E3 or E2 elements of the ubiquitination system, wherein said ubiquitination recognition element has a molecular weight less than 30,000 and has a binding affinity for said E3 and/or E2 elements of the ubiquitination system of at least 102 M−1 and;
• b) a target protein binding element that is able to bind specifically to a target protein wherein said target protein binding element has a molecular weight of less than 30,000 and has a binding affinity for said target protein greater than 105 M−1,
• wherein said ubiquitination recognition element is covalently linked to said target protein binding element.

A method of generating a compound for activating ubiquitination of a target protein which comprises covalently linking a target protein binding element to a ubiquitination recognition element.

A ubiquitination recognition element comprising at least one structural element selected from the group consisting of compound Z, Arg-εAhx-linker, Arg-β-Ala-εAhx-linker, Arg-εAhx-εAhx-linker, Phe-εAhx-linker, Phe-β-Ala-εAhx-linker, Phe-εAhx-εAhx-linker, Arg-Ala-εAhx-linker, Arg-Ala-β-Ala-εAhx-linker, Arg-Ala-εAhx-εAhx-linker, Phe-Ala-εAhx-linker, Phe-Ala-β-Ala-εAhx-linker, Phe-Ala-εAhx-εAhx-linker.