Abstract: We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.

Abstract: Bifunctional molecules and methods for their use in the production of binary complexes in a host are provided. The bifunctional molecule is a conjugate of a drug moiety and a presenter protein ligand. In the subject methods, an effective amount of the bifunctional molecule is administered to the host. The bifunctional molecule binds to the presenter protein to produce a binary complex that exhibits at least one of improved affinity, specificity or selectivity as compared to the corresponding free drug. The subject methods and compositions find use in a variety of therapeutic applications.

Abstract: Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins. In principle, any two target proteins can be induced to associate by treating the cells or organisms that harbor them with cell permeable, synthetic ligands.

Abstract: We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.

Abstract: Bifunctional molecules and methods for their use are provided. The subject bifunctional molecules are conjugates of a drug moiety and a pharmacokinetic modulating moiety, where these two moieties are optionally joined by a linking group. The bifunctional molecules are further characterized in that they exhibit at least one modulated pharmacokinetic property upon administration to a host as compared to a free drug control. The subject bifunctional molecules find use in a variety of therapeutic applications.

Abstract: Bifunctional molecules and methods for their use in the production of binary complexes in a host are provided. The bifunctional molecule is a conjugate of a drug moiety and a presenter protein ligand. In the subject methods, an effective amount of the bifunctional molecule is administered to the host. The bifunctional molecule binds to the presenter protein to produce a binary complex that exhibits at least one of improved affinity, specificity or selectivity as compared to the corresponding free drug. The subject methods and compositions find use in a variety of therapeutic applications.

Abstract: Bifunctional molecules and methods for their use in the production of binary or tripartite complexes in a host are provided. The bifunctional molecule is a conjugate of a drug moiety and a presenter protein ligand. The molecular weight of the bifunctional molecule is less than about 5000 daltons. In the methods, an effective amount of the bifunctional molecule is administered to the host. In certain embodiments the bifunctional molecule binds to the presenter protein and a drug target to produce a tripartite complex, while in other embodiments the bifunctional molecule binds to either the presenter protein or the drug target, but not both, to produce a binary complex The subject methods and compositions find use in a variety of therapeutic applications.

Abstract: We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells

Abstract: Bifunctional molecules and methods for their use in the production of binary complexes in a host are provided. The bifunctional molecule is a conjugate of a drug moiety and a presenter protein ligand. In the subject methods, an effective amount of the bifunctional molecule is administered to the host. The bifunctional molecule binds to the presenter protein to produce a binary complex that exhibits at least one of improved affinity, specificity or selectivity as compared to the corresponding free drug. The subject methods and compositions find use in a variety of therapeutic applications.

Abstract: Bifunctional molecules and methods for their use in the production of binary complexes in a host are provided. The bifunctional molecule is a conjugate of a drug moiety and a presenter protein ligand. The molecular weight of the bifunctional molecule is preferably less than about 5000 daltons, and the drug moiety may have a molecular weight of from about 50 to 2000 daltons. The drug moiety and presenter protein ligand may be covalently linked directly or through a linking group. The drug moiety binds to a drug target such as a protein and the presenter protein ligand binds to a presenter protein that is not the drug target such as extracellular or intracellular protein. Presenter proteins include peptidyl prolyl isomerase (FKBP), Heat Shock Protein 90 (Hsp90), steroid hormone receptors, cytoskeletal proteins, albumin and vitamin receptors.

Abstract: We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.