Abstract: Processes for preparing compounds of Formula (1) and Formula (2) are described, wherein X, Y, Z, R1-R7, L and n are defined herein. Intermediates useful in the preparation of the compounds of Formula (1) and Formula (2) are also described.

Abstract: Selectively controllable cleavable linkers include electrochemically-cleavable linkers, photolabile linkers, thermolabile linkers, chemically-labile linkers, and enzymatically-cleavable linkers. Selective cleavage of individual linkers may be controlled by changing local conditions. Local conditions may be changed by activating electrodes in proximity to the linkers, exposing the linkers to light, heating the linkers, or applying chemicals. Selective cleaving of enzymatically-cleavable linkers may be controlled by designing the sequences of different sets of the individual linkers to respond to different enzymes. Cleavable linkers may be used to attach polymers to a solid substrate. Selective cleavage of the linkers enables release of specific polymers from the solid substrate. Cleavable linkers may also be used to attach protecting groups to the ends of growing polymers. The protecting groups may be selectively removed by cleavage of the linkers to enable growth of specific polymers.

Abstract: Cyclic depsipeptide-class molecules, referred to herein as persephacins (including analogs thereof), having similarities to aureobasidin A, are described. The persephacins have antimicrobial activity, such as antifungal activity against a diverse range of clinically-relevant fungal pathogens, antiprotozoan parasite activity, and antibacterial activity, and can be used for example in treatments of difficult-to-treat ocular fungal infections at lower concentrations than natamycin. The active compounds may be combined with a secondary compound in a composition.

Abstract: Disclosed herein, inter alia, are methods of use and composition of novel inhibitors that target the Smac binding site of a variety of inhibitor of apoptosis proteins that contain a Bir domain, including XIAP, cIAP1, cIAP2, or other IAP proteins.

Abstract: The present invention provides novel compounds comprising an antigen of AML cells, and uses thereof.

Abstract: A microbial infection in an eye of a subject is treated or prevented by topically administering to the eye an effective amount of a macromolecule or a pharmaceutically acceptable salt thereof that includes a dendrimer of 1 to 8 generations with one or more sulfonic acid- or sulfonate-containing moieties attached to one or more surface groups of the outermost generation of the dendrimer. Compositions containing the macromolecule or salt are useful in these methods.

Abstract: Nanostructures having a core, a lipid layer and a lipoprotein which are useful for delivering therapeutic agents are provided herein. Methods of treating disease using the nanostructures are also provided, including methods of treating cancer, infectious disease, vascular disease etc.

Abstract: Disclosed are methods for the synthesis of chiral alcohols by Sortase A-mediated oxidoreductase oligomers, which relates to the field of biocatalysis. In the present disclosure, oxidoreductase oligomers were used as biocatalysts for chiral alcohol preparation. Compared to wild-type enzymes, the oxidoreductase oligomers significantly improved catalytic activity and thermal stability. The sortase A-mediated oxidoreductase oligomers had 6-8 folds improvement in specific activity over that of the wild-type enzymes. The oligomers displayed a Tm value 6-12° C. higher than that of the wild-type, suggesting the sortase A-mediated oxidoreductase oligomers significantly improved thermostability of the enzymes. The oxidoreductase oligomers catalyzed asymmetric transformation to produce (S)-1-phenyl-1,2-ethanediol or (R)-1-phenethyl alcohol within 3-6 hr, with an optical purity of 98%-100% and a yield of 98%-99%.

Abstract: Compositions and processes are provided for the robust detection of hepatitis C virus in a sample. Compositions include amino acid sequences of HCV core region including or exclusive to residues 14-31 or 50-90 of the HCV core protein. Also provided are processes of detecting HCV in a sample whereby the provided peptides are optionally used alone or in conjunction with antibodies that do not recognize the peptides so that detection is independent of seroconversion in a subject. Using the compositions and processes, HCV can be detected in a sample prior to or following seroconversion leading to robust HCV detection and diagnosis.

Abstract: The purpose of the present invention is to provide a polymeric compound in which a camptothecin compound and an anti-cancer effect enhancer, particularly a PARP inhibitor, are bound to a single molecule, whereby it becomes possible to reduce the toxicity to normal cells and deliver and release the two components to an affected area with high efficiency to thereby improve the pharmacological efficacy of the two components. Provided is a polymeric compound represented by general formula (1).

Abstract: The present invention provides polypeptide inhibitors of HSP27 kinase, compositions thereof, and methods for using such polypeptides and compositions for various therapeutic uses.

Abstract: The invention provides methods for attaching drugs, dyes or radiolabels to bis-MTX. This method can be used to prepare bis-MTX analogs that can be used to deliver agents, such as nanoparticles, drugs, dyes or radiolabels, to cells.

Abstract: The present invention relates to a recombinant polypeptide capable of binding to IgE from subjects allergic to venom of an insect from the order Hymenoptera having a homology of more than 70% to the amino acid sequence of SEQ ID NO: 2, which is the honey bee allergen Api m3 (acid phosphatase). The invention further relates to nucleic acid encoding the polypeptide, expression vectors, host cells and methods of preparing the polypeptide, as well as diagnostic and pharmaceutical uses thereof.

Abstract: The purpose of the present invention is to provide a novel method for producing cereulide and a derivative thereof; an intermediate for cereulide; and a novel cereulide derivative. A novel didepsipeptide, a novel tetradepsipeptide, a novel octadepsipeptide and a novel dodecadepsipeptide are prepared. A linear precursor of cereulide or a derivative thereof, which is composed of any one of the novel depsipeptides, is cyclized by forming an intramolecular amide bond.

Abstract: The objective of the present invention is to provide a method for producing a polymer of a monomer having a vinyl group while reducing a residual amount of a surfactant within the polymer as the target compound and waste water. The method for producing a polymer according to the present invention is characterized in comprising the step of polymerizing a monomer having a vinyl group in an aqueous medium in the presence of a surfactin salt, which is a natural peptide surfactant, and a polymerization initiator, wherein a ratio of the surfactin salt (I) to 100 parts by mass of the monomer is not less than 0.0005 parts by mass and less than 0.1 parts by mass.

Abstract: The present invention relates to compounds of the formula (I) and in particular medicaments comprising at least one compound of the formula (I) for use in the treatment and/or prophylaxis of physiological and/or pathophysiological states in the triggering of which cathepsin D is involved, in particular for use in the treatment and/or prophylaxis of arthrosis, traumatic cartilage injuries, arthritis, pain, allodynia or hyperalgesia.

Abstract: The present invention relates to polyamide compositions and therapies for treating cells infected with papilloma virus (PV).

Abstract: The invention relates to a method or process for the chemical manufacture of depsipeptides of the formula I employing an aldehyde acetal intermediate, wherein the symbols have the meaning defined in the description, to new intermediates and their manufacture, as well as related invention embodiments.

Abstract: The present invention includes a novel class of highly specific protease inhibitors. In one embodiment, the inhibitors of the invention are ?-helical in structure. In another embodiment, the present invention represents the first demonstration of a highly specific cysteine protease inhibitor.

Abstract: Disclosed embodiments concern a method for making substantial quantities of desired macrocycles. Disclosed ring closing reactions make the macrocycle with desired olefin geometry in excellent yield and E/Z ratio. Particular embodiments of the current method concern intermediates that are obtained from commercially available starting materials in a small number of steps, thereby illustrating the commercial importance and applicability of the disclosed method. The macrocycle produced by the ring closing reaction can be further derivatized to provide analogs of the macrocyclic compounds.

Abstract: A method for the synthesis of daptomycin or a daptomycin analogue is carried out on a resin to form a linear precursor followed by a serine ligation macrocyclization in solution. Daptomycin analogues can differ from daptomycin by substitution of amino acids residues and/or deletion or addition of amino acid residues. Daptomycin analogues can include a different fatty acid in the side arm of the daptomycin analogue.

Abstract: The present invention relates to novel fluorinated macrocyclic compounds and methods of treating a hepatitis C infection in a subject in need of such therapy with said macrocyclic compounds. The present invention further relates to pharmaceutical compositions comprising the compounds of the present invention, or pharmaceutically acceptable salts, esters, or prodrugs thereof, in combination with a pharmaceutically acceptable carrier or excipient.

Abstract: Disclosed herein are novel synthetic prostate specific antigen (PSA)-targeted capture agents that specifically bind PSA. In certain embodiments, these PSA capture agents are biligand or triligand capture agents containing two or three target-binding moieties, respectively.

Abstract: This invention provides new cyclic lipopeptide antibiotic Locillomycin (Locillomycin-A, Locillomycin-B, Locillomycin-C) that display very strong antifungal, antibacterial, antivirus activities in a variety of contexts in vitro; methods of making and using the compounds, wherein Locillomycin-A, Locillomycin-B and Locillomycin-C are derived and purified from the culture of Bacillus subtilis Bs916.

Abstract: Glucagon analogs are disclosed that exhibit both glucagon antagonist and GLP-1 agonist activity. In one embodiment, the glucagon antagonist/GLP-1 agonist comprises a modified amino acid sequence of native glucagon, in which the first one to five N-terminal amino acids of native glucagon is deleted and in which the alpha helix is stabilized.

Abstract: The invention relates to novel cyclic compounds (cyclic peptides), linkers useful as beta-turn promoters in cyclic peptides, and methods for treatment of malignant cells in vitro or in vivo using one or more linear and cyclic peptides. The peptides can act as integrin interaction inhibitors and may be used in the treatment of cancers as monotherapies or in combination with other anti-cancer agents, such as proteasome inhibitors, inhibitors of autophagy, alkylating agents, MEK inhibitors, FAK/PYK2 inhibitors, and EGFR inhibitors. The invention further concerns a method of predicting the binding of a cyclic or linear HYD1 peptide to a cancer cell by assessing overexpression of biomarkers such as CD44, VLA-4 integrin, basigin, CD138 (syndecan 1), NCAM, ICAM1, ICAM3, and CD59.

Abstract: The purpose of the present invention is to provide a cross-linked peptide containing a novel non-peptide cross-linked structure, and a method for synthesizing the same. A cross-linked peptide having a novel non-peptide cross-linked structure, a useful intermediate for synthesizing the cross-linked peptide, and a method for synthesizing the novel cross-linked peptide and the intermediate are provided. The cross-linked peptide is characterized by having an —NR— bond in the cross-linked structure. By using the method for synthesizing the cross-linked peptide, a cross-link can be freely designed and an change can be freely made to a cross-link.

Abstract: The present invention provides macrocyclic compounds of Formula (I): pharmaceutically acceptable salts thereof; and pharmaceutical compositions thereof, wherein R1, R2, R3, R4, RE, RF, RG, RH, RI, f, g, h, n, and m are as defined herein. The present invention further provides methods of synthesizing these macrocyclic compounds, and methods of their use and treatment. Certain aspects of the present invention relate to modulation of kinase activity, and in the treatment of kinase-associated diseases or disorders.

Abstract: Provided herein are biodegradable copolymers and nanoplex delivery systems comprising the same and a cargo molecule, such as a nucleic acid, a polynucleotide or other biomolecule. The biodegradable copolymers may comprise a reducible polymer linearly modified with lysine, such as a linear lysine-modified N,N?-cystamine bisacrylamide. The biodegradable copolymers also may be conjugated to a sequestering moiety, such as dietheylamine. The biodegradable copolymers also may comprise one or both of a targeting moiety and one or more moieties to facilitate endosomal escape. Also provided are methods for treating a pathophysiological condition and for increasing biocompatibility of a polymeric delivery system upon delivery to a subject using the biodegradable copolymers and nanoplexes.

Abstract: At least some embodiments of the invention relates to an implant having a coating that contains or is composed of a functionalized RGD peptidomimetic RGD-P1 having the formula (1) and/or a functionalized RGD peptidomimetic RGD-P2 having the formula (2), and an associated manufacturing method.

Abstract: 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.

Abstract: The present invention provides a multimeric form of a Tie 2 binding peptide monomer, wherein the multimeric form has Tie 2 agonist activity. The multimeric form, preferably a tetramer, stimulates angiogenesis and promotes wound healing. The present invention also features pharmaceutical compositions comprising the multimeric Tie 2 agonists, including those suitable for topical or systemic administration. Methods of using the multimeric Tie 2 agonists of the invention for stimulating angiogenesis and for promoting healing of wounds, such as diabetic ulcers or skin grafts, are also provided.

Abstract: Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectrum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.

Abstract: In general, the invention relates to methods of synthesizing AbA derivatives that are useful for treating infection and amenable to further chemical elaboration. These novel methods are scalable for industrial production and employ safer, simpler, and more efficient process conditions. Furthermore, the invention also provides novel compounds and intermediates useful for implementing the methods described herein and/or for the treatment of infection.

Abstract: The invention relates to methods for treating human amyloid disease by administration of modified A? peptide immunogens.

Abstract: The present invention provides immunosuppression compounds capable of inhibiting the programmed cell death 1 (PD1) signalling pathway. The present invention further provides peptide based compositions for treatment of cancer or treatment of infections via immunopotentiation caused by inhibition of immunosuppressive signaling induced by PD-1, PD-L1, or PD-L2 and therapies using them, immunopotentiative substrates included as the active ingredient. Further, the invention provides an application of the compositions containing the peptide moieties for preventive and/or therapeutic agents for cancer, cancer metastasis, immunodeficiency, an infectious disease or the like and an application of peptide moieties as a testing or diagnostic agent or a research agent for such a disease.

Abstract: The invention relates to methods for effecting qualitative and quantitative changes in the functional moieties expressed at the surface of cells and multi-cellular structures, and functional lipid constructs for use in such methods. In particular, the invention relates to functional lipid constructs and their use in diagnostic and therapeutic applications, including serodiagnosis, where the functional moiety is a carbohydrate, peptide, chemically reactive group, conjugator or fluorophore.

Abstract: The present invention is method for non-covalently immobilizing an infectious prion protein using a magnetic substrate.

Abstract: A compound of Formula I or a salt thereof, methods for the preparation thereof, and related methods and compositions.

Abstract: The present disclosure provides solid forms of a compound of formula I. In some embodiments, the present disclosure provides crystalline forms of Compound I. In some embodiments, the present disclosure provides solvate forms of Compound I. In some embodiments, the present disclosure provides amorphous Compound I.

Abstract: Methods are disclosed for determining progression of a condition, onset of a condition, or efficacy of treatment of a condition characterized by an adipocyte imbalance in a patient. In addition, methods are disclosed of treating diabetes, abnormal adipocyte activity, and insulin resistance using monomeric, homodimeric, and heterodimeric forms of certain C-terminal fragments of adiponectin receptor. In addition, methods of treating abnormal adipocyte activity, treating metabolic syndrome, causing insulin secretion, increasing insulin levels, inhibiting insulin degradation enzyme, treating Alzheimer's disease, treating cardiovascular disease associated with adiponectin levels, inhibiting ADAM-17 enzyme, inhibiting a protease, treating a condition associated with TNF-alpha, and treating a condition associated with HER2-neu are disclosed. Compositions, dosage forms, and kits are also disclosed.

Abstract: The invention relates to truncated GLP-1 analogues, in particular a GLP-1 analogue which is a modified GLP-1(7-35) (SEQ ID No 1) having: i) a total of 2, 3, 4, 5 6, 7, 8, or 9 amino acid substitutions as compared to GLP-1(7-35), including a) a Glu residue at a position equivalent to position 22 of GLP-1(7-35), and b) an Arg residue at a position equivalent to position 26 of GLP-1(7-35); as well as derivatives thereof, and therapeutic uses and compositions. These analogues and derivatives are highly potent, have a good binding affinity to the GLP-1 receptor, also to the extracellular domain of the GLP-1 receptor, which is of potential relevance achieving long-acting, stable GLP-1 compounds with a potential for once weekly administration.

Abstract: The present invention describes peptide drugs that inhibit the interaction between CAL and CFTR, and other proteins in cystic fibrosis and other diseases. These invented drugs have been chemically optimized to impart solubility, stability, cell permeability, mucus penetration, intracellular targeting and sequestration, increased potency and non-immunogenicity, while conserving and imparting efficacy. This renders these compositions suitable for human use, which is exemplified by use in the treatment of cystic fibrosis.

Abstract: The invention relates to disulfide-rich dimer molecules which inhibit binding of ?4?7 to the mucosal addressin cell adhesion molecule (MAdCAM) in vivo, and show high selectivity against ?4?1 binding.

Abstract: The objective of the present invention is to provide an extinguishing agent which has excellent fire-extinguishing property and which exhibits high safety to the environment and human body. The fire extinguishing agent of the present invention is characterized in comprising a biosurfactant.

Abstract: The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

Abstract: The disclosure relates to the field of candidate drug testing and drug development. Described are methods for providing a compound composed of at least one molecule attached via at least two linkages to a molecular scaffold, the method comprising providing a scaffold comprising at least a first and a second reactive group; providing at least one molecule able to react with the at least first and second reactive group; and contacting the scaffold with at least one molecule to form at least two linkages between the scaffold and the molecule in a coupling reaction, wherein the formation of a linkage accelerates the formation of a consecutive linkage. The coupling reaction may be performed in solution, such as an aqueous solution. Furthermore, described is a method for selecting a candidate drug compound comprising providing a library of the compounds and determining the binding of a target molecule to the compounds.

Abstract: The present invention provides novel peptidomimetics, of formula (I), which primarily act as glucose dependent insulin secretagogues. Furthermore, it was found that these peptidomimetics showed glucagon receptor antagonistic activity, along with the GLP-1 receptor agonistic activity.

Abstract: The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

Abstract: At least some embodiments of the invention relates to an implant having a coating that contains or is composed of a functionalized RGD peptidomimetic RGD-P1 having the formula (1) and/or a functionalized RGD peptidomimetic RGD-P2 having the formula (2), and an associated manufacturing method.