Abstract: The present invention relates to derivatives of the sesquiterpene lactone micheliolide, methods and compositions for their preparation, and methods for using the micheliolide derivatives in pharmaceutical compositions as anticancer and anti-inflammatory agents. The invention also relates to methods for producing micheliolide derivatives modified at positions C2 and C14. The invention also relates to methods for producing parthenolide derivatives modified at positions C2 and C14 in conjunction with modifications at position C13, via chemoenzymatic methods. The invention further relates to methods for using parthenolide derivatives for treating cancer and inflammatory diseases.

Abstract: This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.

Abstract: This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.

Abstract: Cyclic peptide compounds are provided that can bind to one or more homologs of Hedghehog signaling proteins and block their interaction with the Patched receptor. These compounds are useful for suppressing Hedgehog-dependent stimulation of the Hedgehog pathway in cells and in living organisms. Methods for using the cyclic peptide compounds, and compositions comprising them, for treatment of cancers and other diseases which are characterized by aberrant Hedgehog-dependent activation of the Hedgehog pathway and/or which can benefit from chemical suppression of Hedgehog-dependent signaling are also disclosed.

Abstract: This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.

Abstract: Methods and compositions are provided for the display of genetically encoded macrocyclic peptides on a biological surface. Also provided are nucleic acid molecules, polypeptides, and methods for generating combinatorial libraries of macrocyclic peptides displayed on a biological surface. These methods can be used to produce and screen vast libraries of conformationally constrained peptides in a high-throuput manner, from which macrocyclic peptides with a desired property can be selected and identified.

Abstract: The present invention relates to derivatives of the sesquiterpene lactone micheliolide, methods and compositions for their preparation, and methods for using the micheliolide derivatives in pharmaceutical compositions as anticancer and anti-inflammatory agents. The invention also relates to methods for producing micheliolide derivatives modified at positions C2 and C14. The invention also relates to methods for producing parthenolide derivatives modified at positions C2 and C14 in conjunction with modifications at position C13, via chemoenzymatic methods. The invention further relates to methods for using parthenolide derivatives for treating cancer and inflammatory diseases.

Abstract: This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.

Abstract: Methods and compositions are provided for generating macrocyclic peptides from genetically encoded, ribosomally produced polypeptide precursors. Also provided are nucleic acid molecules, polypeptides, and methods for generating combinatorial libraries of macrocyclic peptides. These methods can be used to produce vast libraries of conformationally constrained peptide ligands as well as facilitate the functional screening of these libraries to identify compound(s) with desired activity properties.

Abstract: Derivatives of the antimalarial agent artemisinin, compositions comprising the derivatives, methods for preparing the derivatives, and their uses in pharmaceutical compositions intended for the treatment of parasitic infections are provided. Methods are provided for the production of artemisinin derivatives via functionalization of positions C7 and C6a, and optionally, in conjunction with modifications at positions C10 and C9, via chemoenzymatic methods. Recombinant cytochrome P450 polypeptides are also provided for use in the methods. The artemisinin derivatives can be used for the treatment of malaria and other parasitic infections, alone or in combination with other antiparasitic drugs.

Abstract: Cyclic peptide compounds are provided that can bind to one or more homologs of Hedghehog signaling proteins and block their interaction with the Patched receptor. These compounds are useful for suppressing Hedgehog-dependent stimulation of the Hedgehog pathway in cells and in living organisms. Methods for using the cyclic peptide compounds, and compositions comprising them, for treatment of cancers and other diseases which are characterized by aberrant Hedgehog-dependent activation of the Hedgehog pathway and/or which can benefit from chemical suppression of Hedgehog-dependent signaling are also disclosed.

Abstract: Methods and compositions are provided for generating macrocyclic peptides constrained by side-chain-to-C-terminus non-peptidic tethers for use as functional and structural mimics of ?-helical motifs, including in therapeutic applications. These methods can be used to produce libraries of conformationally constrained peptidomimetics to identify compounds with desired activity properties.

Abstract: The invention provides compositions and methods for inhibiting protein-protein interactions with cap-binding protein 80 (CBP80). In one embodiment, the invention provides compositions comprising linear and macrocylic peptides. In one embodiment, the invention provides methods for treating cancer, heart disease, autoimmune disorders, obesity, diabetes, or chronic inflammation disorders associated with the PGC1 family of co-activators.

Abstract: This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.

Abstract: This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.

Abstract: Derivatives of the antimalarial agent artemisinin, compositions comprising the derivatives, methods for preparing the derivatives, and their uses in pharmaceutical compositions intended for the treatment of parasitic infections are provided. Methods are provided for the production of artemisinin derivatives via functionalization of positions C7 and C6a, and optionally, in conjunction with modifications at positions C10 and C9, via chemoenzymatic methods. Recombinant cytochrome P450 polypeptides are also provided for use in the methods. The artemisinin derivatives can be used for the treatment of malaria and other parasitic infections, alone or in combination with other antiparasitic drugs.

Abstract: This invention relates to modified hydroxylases. The invention further relates to cells expressing such modified hydroxylases and methods of producing hydroxylated alkanes by contacting a suitable substrate with such cells.

Abstract: Methods and compositions are provided for covalently linking a chemical species to a recombinant or synthetic polypeptide. The methods involve the reaction of a thioester-comprising polypeptide with a reagent comprising a reactive amino-thiol group connected to the chemical species which is to be covalently linked to the polypeptide, via a linker. Such chemical species can be a functional group, a label or tag molecule, a biological molecule, a ligand, or a solid support. Efficient and catalyst-free methods for C-terminal protein labeling are also provided. The methods expand current capabilities in the area of protein functionalization, providing useful and complementary tools for the isolation, detection, characterization, and analysis of proteins in a variety of in vitro and in vivo applications.

Abstract: Derivatives of the antimalarial agent artemisinin, compositions comprising the derivatives, methods for preparing the derivatives, and their uses in pharmaceutical compositions intended for the treatment of parasitic infections are provided. Methods are provided for the production of artemisinin derivatives via functionalization of positions C7 and C6a, and optionally, in conjunction with modifications at positions C10 and C9, via chemoenzymatic methods. Recombinant cytochrome P450 polypeptides are also provided for use in the methods. The artemisinin derivatives can be used for the treatment of malaria and other parasitic infections, alone or in combination with other antiparasitic drugs.

Abstract: Methods and compositions are provided for generating macrocyclic peptides constrained by side-chain-to-C-terminus non-peptidic tethers for use as functional and structural mimics of ?-helical motifs, including in therapeutic applications. These methods can be used to produce libraries of conformationally constrained peptidomimetics to identify compounds with desired activity properties.