Abstract: The present invention relates to a branched peptide that includes a first peptide chain and a second peptide chain having its C-terminal amino acid covalently linked to a sidechain of an amino acid residue of the first peptide chain, wherein the first peptide chain includes a plurality of aromatic amino acids and, optionally, an aromatic group linked to an amino terminus of the first peptide chain; and the second peptide chain includes a plurality of hydrophilic amino acids and an enzyme cleavage site. Pharmaceutical compositions containing the branched peptide and one or more therapeutic agents in an aqueous medium are disclosed, where the branched peptides form micelle structures in the aqueous medium. Methods of using the pharmaceutical composition to deliver therapeutic agents, and for treating various disease conditions are also described.

Abstract: The present invention relates generally to novel depsipeptides, to methods for the preparation of these novel depsipeptides, to pharmaceutical compositions comprising the novel depsipeptides; and to methods of using the novel depsipeptides to treat or inhibit various disorders.

Abstract: This invention relates to compositions including antibacterial compounds. The invention also relates to the use of the compositions in methods of treating bacterial infections. In one aspect the present invention also provides a method of increasing the susceptibility of bacteria to the anti-bacterial activity of a compound, the method comprising contacting the bacteria with a star shaped peptide polymer of the invention, thereby increasing the susceptibility of the bacteria to the anti-bacterial activity of the compound. Preferably, the method further includes the step of contacting the bacteria with the compound for which the bacteria have increased susceptibility to. The invention is further relates to the combination of a star shaped peptide polymer and an anti-bacterial compound that restore the sensitivity of antibiotic resistant bacteria to antibiotics that are otherwise ineffective when administered alone.

Abstract: Disclosed is a polypeptide binding to a plurality of amyloid monomers and aggregates, characterised in that: the polypeptide contains the amino acid sequences as shown in (a) and/or (b): (a) the general formula of the amino acid sequence is Ser-X1-Phe-X2-Asn-Lys-Arg, wherein X1 and X2 are independently any one of the 20 amino acids; and (b) the variant having the function of the polypeptide and modifying the general formula (a) of the amino acid sequence by the substitution, deletion or addition of one or more amino acid residues.

Abstract: Provided herein are stabilized peptides that bind Mcl-1. Also provided are compositions containing these polypeptides and methods of using such peptides in the treatment of cancer that include administering to a subject one of the polypeptides.

Abstract: New improved formulations are described, comprising at least one composition, with or without another composition, in which the at least one composition is an inhibitor of lipid A deacetylase resulting in permeabilization of an outer membrane of a susceptible microorganism to which it is provided to. The another composition is a streptogramin. Said at least one composition, alone or in combination, may be used to improve and/or treat a wide variety of bacterial infections, providing better efficacy, bioavailability, and/or pharmacokinetics, as compared with at least other or alternative inhibitors of lipid A deacetylase. When provided to a susceptible microorganism as a combination described herein, of the at least one composition and the another composition, the combination may be provided independently or may be provided together (co-combined in a same formulation, or in different formulations).

Abstract: Pharmaceutical compositions are provided for extending the serum half-life of a therapeutic agent. The composition may include a strained alkyne-labeled therapeutic agent. Also provided is a strained alkyne-carrier protein adduct including a vinyl thioether-linkage to a cysteine residue of the carrier protein. Methods of chemoselectively modifying a carrier protein are provided, that include conjugating a cysteine residue of a carrier protein with a cyclooctyne-labeled cargo agent to produce a vinyl thioether-linked conjugate. Also provided is a method of increasing the in vivo half-life of a bioactive agent including administering a strained alkyne-labeled bioactive agent to a subject.

Abstract: A linker peptide for constructing a fusion protein. The linker peptide comprises a flexible peptide and a rigid peptide. The flexible peptide consists of one or more flexible units. The rigid peptide consists of one or more rigid units. The flexible unit comprises two or more amino acid residues selected from Gly, Ser, Ala, and Thr. The rigid unit comprises a human chorionic gonadotropin ?-subunit carboxy-terminal peptide (CTP) bearing a plurality of glycosylation sites. The linker peptide can more effectively eliminate mutual steric hindrance of two fusion molecules, decreasing a reduction/loss of polymerization or activity resulting from improper folding of an active protein or a conformational change. On the other hand, the negatively charged, highly sialylated CTP can resist renal clearance, further prolonging a half-life of a fused molecule and enhancing bioavailability of a fused protein.

Abstract: The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to the methods used to identify membrane receptors or transporters capable of carrying cargo specifically targeted to the parenchymal tissue of the brain and to in vivo enrichment methods for selecting peptides that are transported across the blood-brain barrier (“BBB”), or analogously, across other membrane containing organs or structures, such as liver, spleen, kidney and tumors.

Abstract: A mitochondrial-targeted PARP inhibitor is provided herein, as well as methods of making and using the mitochondrial-targeted PARP inhibitor.

Abstract: A group of peptide compounds and their use in identifying molecules that stimulate proteasome or immunoproteasome are disclosed herein.

Abstract: The invention provides materials and methods for the treatment of obesity and excess weight, diabetes, and other associated metabolic disorders. In particular, the invention provides novel acylated glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: The present invention relates to a process for the purification of compound of formula II, wherein X may be independently selected from trifluoroacetic acid, hydrochloric acid, hydrobromic acid, p-toluene sulfonic acid and phosphoric acid; its isolation as solid and use for the preparation of carfilzomib.

Abstract: Analogues of an alternatively spliced form of atrial natriuretic peptide (MANP) that exhibit pGC-A gain of function and can be used to treat cardiorenal and metabolic disease are described herein.

Abstract: The invention relates to the compound of general formula (I) as novel inhibitors of transglutaminases, to methods for producing the inventive compounds, to pharmaceutical compositions containing said inventive compounds and to their use for the prophylaxis and treatment of diseases associated with transglutaminases.

Abstract: This disclosure relates to recombinant or chimeric FVIII proteins, variants, and vectors encoding the proteins containing one or more ancestral mutations. In certain embodiments, one or more protein domains comprise amino acid sequences that are derived from ancestrally reconstructed amino acid sequences. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising the proteins or vectors and related methods of inducing blood clotting.

Abstract: This invention relates to a conjugate of formula (I): (A-Z1-)n-Q-Z2-D (I), wherein Z1, Z2, Q, A, D, and n are as described herein. This invention also relates to a pharmaceutical composition including a pharmaceutically acceptable carrier and a conjugate of formula (I). This invention also relates to a method making a conjugate of formula (I), and the use of the conjugate for treating cancerous conditions, modulating cell membrane microheterogeneity, stimulating an immunoresponse, and forming a network on or near the inner or outer surface of target cells.

Abstract: Analogs for CLR/RAMP receptor ligands are provided that have agonist, superagonist, antagonist or superantagonist activity. The analogs can be selective for one or more CLR/RAMP receptors, or can be pan-specific.

Abstract: Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.

Abstract: Disclosed are methods and compositions for the treatment of a proliferative disorder characterized by increased expression of the FOXM1 gene. Exemplary disorders include adenocarcinoma, melanoma, rhabdomyosarcoma, non-small cell lung cancer (NSCLC), head and neck squamous carcinoma, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, colon carcinoma, basal cell carcinoma, infiltrating ductal breast carcinoma, anaplastic astrocytoma, glioblastoma, pancreatic carcinoma, gastric cancer, acute myeloid leukemia, lung cancer, liver cancer, breast cancer, prostate cancer, a brain cancer. Kits and articles of manufacture comprising compositions for such treatment are also disclosed.