Proteolysis targeting chimeric pharmaceutical
The present invention is based on the discovery of a composition that provides targeted ubiquitination. Specifically the composition contains an ubiquitin pathway protein binding moiety which recognizes an ubiquitin pathway protein and a targeting moiety which recognizes a target protein. In addition, the present invention provides libraries of compositions, where each composition contains an ubiquitin pathway protein binding moiety and a member of a molecular library. The libraries of the present invention can be used to identify proteins involved in a predetermined function of cells.
1. A composition comprising:
a) a ubiquitin pathway protein binding moiety, wherein the ubiquitin pathway binding moiety is IkB-alpha or an IkB-alpha peptide; and
b) a target protein binding moiety covalently coupled to the ubiquitin pathway protein moiety of a), wherein the target protein binding moiety is ovalicin.
2. The composition according to claim 1 , wherein the composition binds methionine amino-peptidase 2 (MetAP 2).
3. The composition of claim 1 , wherein the ubiquitin pathway binding moiety is an IkB-alpha peptide.
4. The composition of claim 3 , wherein the IkB-alpha peptide is as set forth in SEQ ID NO: 1.