Abstract: The invention provides an improved process for preparing romidepsin. The process involves producing, purifying, or storing romidepsin under conditions that prevent the formation of undesired adducts. Purifying romidepsin at an apparent pH lower than approximately 6.0 (e.g., between an apparent pH of 4.0 and 6.0) has been discovered to prevent the reduction of the disulfide bond of romidepsin and the subsequent formation of dimerized, oligomerized, or polymerized adducts. The invention also provides pharmaceutical compositions of monomeric romidepsin free of dimerized, oligomerized, or polymerized adducts.

Abstract: Described are methods for identifying targets in RNA molecules based on differences in RNA secondary structure related to sequence variances between different allelic forms. Also described are methods for identifying or developing small molecules which can be used to modulate a target RNA by creation of protein-small-molecule-RNA complexes, as well as compositions which include such small molecules and methods of using those small molecules and compositions.

Abstract: Described herein are nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties. Also described herein are methods of making and using nucleic acid prodrugs and nucleic acid prodrugs comprising chiral phosphorous moieties.

Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.

Abstract: The invention relates to bifunctional stapled or stiched peptides comprising a targeting domain, a linker moiety, and an effector domain, that can be used to tether, or to bring into close proximity, at least two cellular entities (e.g., proteins). Certain aspects relate to bifunctional stapled or stiched peptides that bind to an effector biomolecule through the effector domain and bind to a target biomolecule through the targeting domain. Polypeptides and/or polypeptide complexes that are tethered by the bifunctional stapled or stiched peptides of the invention, where the effector polypeptide bound to the effector domain of the bifunctional stapled or stiched peptide modifies or alters the target polypeptide bound to the targeting domain of the bifunctional peptide. Uses of the inventive bifunctional stapled or stiched peptides including methods for treatment of disease (e.g., cancer, inflammatory diseases) are also provided.

Abstract: One object of the present invention is to provide methods and compositions for inhibiting human telomerase, by providing inhibitors that bind to the CR4-CR5 or pseudoknot/template domains of the RNA component of human telomerase.

Abstract: The present invention provides technology for making large (e.g., greater than 50 amino acids), semi-synthetic, stapled or stitched proteins. The method essentially involves ligating a synthetically produced stapled or stitched peptide to a larger protein. Modified version of IL-13 and MYC are provided as illustrative examples.

Abstract: The present invention relates to HDAC inhibitor derivatives, particularly derivatives of the free thiol of metabolites of the HDAC inhibitor FK228, pharmaceutical compositions thereof, and to methods of using such derivatives and pharmaceutical compositions thereof in the treatment of diseases associated with HDAC, in particular, tumor or cell proliferation diseases.

Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.

Abstract: The present invention provides novel stabilized crosslinked compounds having secondary structure motifs, libraries of these novel compounds, and methods for the synthesis of these compounds libraries thereof. The synthesis of these novel stabilized compounds involves (1) synthesizing a peptide from a selected number of natural or non-natural amino acids, wherein said peptide comprises at least two moieties capable of undergoing reaction to promote carbon-carbon bond formation; and (2) contacting said peptide with a reagent to generate at least one crosslinker and to effect stabilization of a secondary structure motif. The present invention, in a preferred embodiment, provides stabilized p53 donor helical peptides. Additionally, the present invention provides methods for disrupting the p53/MDM2 binding interaction comprising (1) providing a crosslinked stabilized ?-helical structure; and (2) contacting said crosslinked stabilized ?-helical structure with MDM2.

Abstract: The present invention provides inventive stitched polypeptides, pharmaceutical compositions thereof, and methods of making and using inventive stitched polypeptides.

Abstract: Novel compounds and compositions including those compounds, as well as methods of using and making the compounds are herein described. The compounds are useful in therapeutic applications, including modulation of disease or disease symptoms in a subject (e.g., mammal, human, dog, cat, horse). The compounds are useful as modulators of the mu opioid receptor (MOR) through their binding affinity with that receptor.

Abstract: Cross-linked peptides related to human p53 and bind to HMD2 or a family member of HDM2 useful for promoting apoptosis, e.g., in the treatment of and identifying therapeutic agents that binding to HMD2 or a family member of HDM2.

Abstract: The invention provides an improved process for preparing romidepsin. The process involves producing, purifying, or storing romidepsin under conditions that prevent the formation of undesired adducts. Purifying romidepsin at an apparent pH lower than approximately 6.0 (e.g., between an apparent pH of 4.0 and 6.0) has been discovered to prevent the reduction of the disulfide bond of romidepsin and the subsequent formation of dimerized, oligomerized, or polymerized adducts. The invention also provides pharmaceutical compositions of monomeric romidepsin free of dimerized, oligomerized, or polymerized adducts.

Abstract: Stably cross-linked a polypeptides related to human MAML are described. These cross-linked polypeptides contain at least two modified amino acids that together form an internal cross-link or tether that can help to stabilize the alpha-helical secondary structure that is thought to be important for binding of MAML peptides to the Notch transcription complex, a complex that includes ICN and CSL.

Abstract: The invention provides an improved process for preparing romidepsin. The process involves producing, purifying, or storing romidepsin under conditions that prevent the formation of undesired adducts. Purifying romidepsin at an apparent pH lower than approximately 6.0 (e.g., between an apparent pH of 4.0 and 6.0) has been discovered to prevent the reduction of the disulfide bond of romidepsin and the subsequent formation of dimerized, oligomerized, or polymerized adducts. The invention also provides compositions of monomeric romidepsin free of dimerized, oligomerized, or polymerized adducts.

Abstract: The invention provides an improved process for preparing romidepsin. The process involves producing, purifying, or storing romidepsin under conditions that prevent the formation of undesired adducts. Purifying romidepsin at an apparent pH lower than approximately 6.0 (e.g., between an apparent pH of 4.0 and 6.0) has been discovered to prevent the reduction of the disulfide bond of romidepsin and the subsequent formation of dimerized, oligomerized, or polymerized adducts. The invention also provides compositions of monomeric romidepsin free of dimerized, oligomerized, or polymerized adducts.

Abstract: Therapeutic conjugates containing a statin or a modified statin (collectively “statin”) linked to a therapeutic agent (also referred to as a drug herein) are targeted to the liver by the statin or modified statin and thereby deliver the therapeutic agent to liver cells.

Abstract: Novel compounds and compositions including those compounds, as well as methods of using and making the compounds are herein described. The compounds are useful in therapeutic applications, including modulation of disease or disease symptoms in a subject (e.g., mammal, human, dog, cat, horse). The compounds are useful as modulators of the mu opioid receptor (MOR) through their binding affinity with that receptor.

Abstract: The present application pertains to products and methods related to the ability of short nucleotide oligomers to bind the tertiary or globular structure of nucleic acids. This application discloses libraries of short oligomers and methods for using these libraries.