Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Disclosed are p53 peptides and their use as biomarkers in the diagnosis and/or prognosis of Alzheimer's disease (AD) in a biological sample. The invention also provides for a diagnostic method based on a highly accurate mass spectrometry analysis for the diagnosis of Alzheimer's disease at the pre-clinical and prodromal stages of the disease and for the prognosis of cognitive decline in a subject, by quantitating the levels of said p53 peptides specifically in human plasma of patients.

Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one CD 122/CD 132 agonist, at least one immune checkpoint inhibitor and a viral composition comprising one or more viruses engineered to overexpress a tumor suppressor gene and/or an adenoviral death protein. Also provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one oncolytic viral composition and at least one CD122/CD132 agonist and at least one immune checkpoint inhibitor. Also provided herein are methods of enhancing anti-tumor efficacy by administering the agents described above in combination with other cancer therapies. In highly aggressive forms of cancer, known to be generally resistant to immune therapies, these treatments unexpectedly resulted in complete tumor remissions and curative outcomes.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and/or clearance in tissues, receptor uptake and/or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and/or modulation of a cell's status, function, and/or activity.

The present disclosure provides pharmaceutical compositions comprising rationally designed peptide analogs of the p65-TAD binding region of GILZ to selectively sequester activated p65. Structural and functional analyses suggest that select GILZ analog (GA) bind p65-TAD with optimum affinity, exhibit an estimated half minimal lethal dose comparable to known peptide drugs and suppress A1-42 induced cytotoxicity. Furthermore, the present disclosure provides uses and methods of using the pharmaceutical compositions, and uses and methods of using pharmaceutical formulations comprising the pharmaceutical compositions, for the treatment of neurodegenerative diseases such as Alzheimer's Disease, Parkinson's Disease, multiple sclerosis, and amyotrophic lateral sclerosis (ALS).

The present invention is in the field of oncology, and more particularly of cancer stem cells. It relates to a method for producing cancer stem cells based on overexpression of 133536 isoform, 13353 isoform, or both 133536 and 13353 isoforms; a method for predicting the risk that treatment with a chemotherapeutic anti-cancer agent induces cancer stem cells in a subject suffering from cancer from a cancer sample of said subject, based on detection of an increase in 133536 isoform, 13353 isoform, or both 133536 and 13353 isoforms following chemotherapeutic anti-cancer treatment; to therapeutic uses of a combination of chemotherapeutic anti-cancer agent and an agent reducing 133p536 isoform, 13353 isoform, or both 133536 and 13353 isoforms expression; and also to screening methods for anti-cancer stem cells agents.

The invention is a novel reporter system for measuring protein-protein interactions. The system uses a pair of functionalized coiled coil subunits that spontaneously form two separate homo-oligomers when expressed in cells. The coiled coil subunits are functionalized with fluorescent proteins and complementary interacting proteins. Upon an activation stimulus which promotes the protein-protein interaction, the interacting proteins drive the formation of multivalent aggregates of the homo-oligomers in phase-shifted droplets. The highly concentrated fluorescent proteins in these structures provide high brightness over background fluorescence and a readily observed, quantitative and dynamic indicator of the protein-protein interaction. The reporters and assay methods are amenable to cells and whole organisms.

Novel mp53 rescue compounds and the pharmaceutical composition, and methods of treating a p53 disorder.

The present invention relates to compositions useful in inhibiting Bcl-XL or MCL-1 and disrupting p53-MDM2 and p53-MDMX interactions, and methods of using those compositions for treating a subject for conditions responsive to increasing p53 mediated activity or promoting p53 independent apoptosis, such as treating cancer. In some aspects, the compositions of this invention relate to fusion polypeptides comprising a human serum polypeptide and a p53-peptide, which can be, in some aspects, a p53 derived peptide and/or a p53 activating peptide.

The invention relates to novel peptides having an HDM-2 targeting sequence that target the human minute binding protein-2. The invention also relates to fusion proteins comprising a HDM-2 targeting sequence. The invention also relates to methods of using the peptides to treat cancer.