Abstract: A system for visually representing peptide sequences includes a memory configured to store instructions and a processor to execute the instructions to perform operations. The operations include receiving data representing a peptide sequence. The data includes an index representing a position for each amino acid in the peptide sequence. The operations further include categorizing each amino acid in the peptide sequence and assigning each amino acid a value associated with the category. The operations additionally include determining relationship groups, each group including two amino acids in the peptide sequence, based upon a geometrical structure of the peptide sequence. The operations also include filtering the relationship groups to remove groups based upon the category of at least one of the two amino acids that make up the group; and producing a visual representation that includes a representation of each amino acid of the filtered relationship groups.

Abstract: This disclosure relates to the surprising and unexpected finding that the well-known cancer protein, Myeloid Cell Leukemia-1 (MCL-1), binds to and modulates the enzymatic activity of Very Long Chain Acyl CoA Dehydrogenase (VLCAD), thereby regulating fatty acid ?-oxidation. This finding is employed in compositions and methods of treating cancer, metabolic diseases, or other conditions characterized by excessive fatty acid ?-oxidation by blocking or reducing the energy production of cells (e.g., cancer) through inhibiting the MCL-1/VLCAD interaction and/or directly inhibiting VLCAD enzymatic activity. In addition, the disclosure features methods for identifying such agents that inhibit the interaction between MCL-1 and VLCAD or that inhibit VLCAD enzymatic activity.

Abstract: Provided herein are peptide-based therapeutics that target FOXP3 and methods of use thereof to decrease the immuno-suppressive effects of Tregs and inhibit immune dysregulation, while sparring inhibition of activated cytotoxic T cells, for example, in the context of anti-tumor immune responses, autoimmunity, inflammatory conditions, etc.

Abstract: Compositions and methods are provided for the treatment or prevention of chemotherapy-induced peripheral neuropathy and hearing loss in a subject in need thereof. The methods involve administering to the subject a bclw protein, a BH4 domain-containing fragment thereof, or a bclw mimetic. Also provided are exemplary bclw mimetics.

Abstract: Disclosed herein are cross-linked peptides either alone or conjugated to PEG(n)-cholesterol (or thiocholesterol) moieties useful for interfering with and inhibiting or preventing coronavirus infection (e.g., infection by SARS-CoV-2). Also disclosed are methods of treating and/or preventing a coronavirus infection (e.g., COVID-19.

Abstract: This disclosure describes stabilized peptides and methods for detecting a biomarker on, outside, or within a live cell or tissue, or in a cell or tissue that has been fixed for an immunological assay or histopathologic evaluation. The present disclosure further describes stabilized peptides and methods for diagnosing and/or monitoring the progression of a disease in a subject, or for monitoring the efficacy of a disease treatment in a subject, based on the presence of a biomarker, the amount of a biomarker, and/or the localization of a biomarker in a live or fixed cell or tissue obtained from a subject.

Abstract: Surgical constructs, assemblies, kits and methods of tissue fixation are disclosed. Glenoid augmentation is conducted with one or more soft tissue grafts placed on the anterior glenoid to fill a glenoid defect. Knotted or knotless suture anchors can deliver and fixate the soft tissue graft within the glenoid bone defect. Suture anchors can also secure the native ligament to the soft tissue graft and provide stability to the shoulder joint. Soft suture anchors can deliver and fixate a soft tissue graft within the bone defect. The native soft tissue can be repaired over top of the soft tissue graft into its anatomical position.

Abstract: Messaging services for providing updates for multimedia content delivered over the Internet for a live event. In one embodiment, a messaging server provides real-time updates for multimedia content of a live event delivered over the Internet to multiple media players that request the multimedia content over the Internet. In one embodiment, the real-time updates indicate when the multimedia content is available for delivery over the Internet. In another embodiment, the real-time updates can be used to dynamically insert advertisement markers for advertisement breaks in the multimedia content.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: Structurally stabilized, e.g., stapled, peptides with the ability to translocate through microbial cell membranes to the interior of microbial cells and exert a biological activity there are provided, as are methods of designing, making and using such peptides.

Abstract: Messaging services for providing updates for multimedia content delivered over the Internet for a live event. In one embodiment, a messaging server provides real-time updates for multimedia content of a live event delivered over the Internet to multiple media players that request the multimedia content over the Internet. In one embodiment, the real-time updates indicate when the multimedia content is available for delivery over the Internet. In another embodiment, the real-time updates can be used to dynamically insert advertisement markers for advertisement breaks in the multimedia content.

Abstract: Provided herein is a platform technology for designing stabilized peptides that covalently bind their target protein and thereby inhibit the activity of the target protein. Also provided are exemplary stabilized peptides that can be used for covalent modification of their target proteins.

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: This disclosure features structurally-stabilized and/or cysteine-reactive peptide inhibitors for selective targeting of BFL-1, or dual targeting of BFL-1 and MCL-1. Also disclosed are methods of using such structurally-stabilized and cysteine-reactive peptides in the treatment of BFL-1- and/or MCL-1-expressing or -dependent cancers or diseases of cellular excess (e.g., autoimmune or inflammatory conditions). Also provided are combination therapies comprising such structurally-stabilized and/or cysteine-reactive peptides and inhibitors of the DNA damage response pathway, such as an ATM kinase inhibitor, ATR kinase inhibitor, CHK1/2 inhibitor, or PARP inhibitor; or an inhibitor of MCL-1, or a selective inhibitor of BCL-2, or an inhibitor of BCL-2/BCL-XL, for the treatment of BFL-1-expressing or -dependent cancers (e.g., AML), BFL-1 and MCL-1-expressing or -dependent cancers, or diseases of cellular excess (e.g., autoimmune or inflammatory conditions).

Abstract: In some embodiments, a mass spectrometry tag may comprise a linker region, a mass balance region, and a reporter region. The mass spectrometry tag may be configured to fragment in a mass spectrometer via an energy dependent process to produce multiple reporter molecules. For example, the reporter region of the tag may be configured to produce at least two reporter molecules via fragmentation. In some embodiments, one or more regions of the tag may comprise at least one heavy isotope. In some such embodiments, the ability to fragment into multiple reporter molecules as well as the placement and/or number of heavy isotope(s) allows the mass spectrometry tag to be distinguished from other similar mass spectrometry tags. In some such embodiments, the ability to distinguish between tags having the same or substantially similar total mass to charge ratio and reporter region mass may allow the system to have a greater multiplexing capacity than conventional systems.

Abstract: The present application describes stapled peptide degron chimeras, which act as protein degradation inducing moieties, either by combining a stapled peptide that binds a disease-related protein with a small molecule degron, such as a cereblon- or VHL-binding small molecule as the degron, or a polypeptide sequence degron, such as a Cop1-binding Trib peptide as the degron; or by combining a stapled peptide degron with a peptide, such as a stapled peptide, or a small molecule that binds a disease-related protein. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of stapled peptide degron chimeras which can be utilized in the treatment of proliferative disorders or other conditions whereby elimination of a disease-causing or disease-related protein would have a therapeutic benefit. The present application also provides methods for making compounds of the application and intermediates thereof.

Abstract: This disclosure features structurally-stabilized and/or cysteine-reactive peptide inhibitors for selective targeting of BFL-1, or dual targeting of BFL-1 and MCL-1. Also disclosed are methods of using such structurally-stabilized and cysteine-reactive peptides in the treatment of BFL-1- and/or MCL-1-expressing or -dependent cancers or diseases of cellular excess (e.g., autoimmune or inflammatory conditions). Also provided are combination therapies comprising such structurally-stabilized and/or cysteine-reactive peptides and inhibitors of the DNA damage response pathway, such as an ATM kinase inhibitor, ATR kinase inhibitor, CHK1/2 inhibitor, or PARP inhibitor; or an inhibitor of MCL-1, or a selective inhibitor of BCL-2, or an inhibitor of BCL-2/BCL-XL, for the treatment of BFL-1-expressing or -dependent cancers (e.g., AML), BFL-1 and MCL-1-expressing or -dependent cancers, or diseases of cellular excess (e.g., autoimmune or inflammatory conditions).

Abstract: Disclosed herein are structurally stabilized peptides of ACE2 helix 1 useful for diagnosing, preventing, and treating coronavirus infection by targeting the receptor binding domain of SARS-CoV-2 and thereby blocking its interaction with the human ACE2 receptor, which is involved in coronavirus infection and pathogenesis.

Abstract: Disclosed herein are cross-linked peptides useful for interfering with and inhibiting coronavirus infection (e.g., infection by SARS-CoV-2). Also disclosed are methods of treating and/or preventing a coronavirus infection (e.g., COVID-19).

Abstract: The disclosure relates to cell-permeable stabilized peptide modules and methods of use for e.g., cellular delivery of cargoes.