Abstract: The present invention relates generally to a molecular framework having a cyclic structure. More particularly, the present invention provides cyclic proteins and derivatives thereof in which particular turns and other elements of the molecular structure are held in defined orientations with respect to each other. The cyclic proteins of the present invention provide a molecular framework for the introduction of particular amino acids or heterologous amino acid sequences to facilitate the presentation of biological activities associated with these heterologous amino acid sequences. The molecular framework of the present invention may be naturally cyclic or may be a cyclized derivative of a linear molecular or may be a linear derivative of a cyclized molecule. The present invention contemplates the use of the molecular framework with or without particular amino acids inserted or substituted thereon for the treatment of or prophylaxis of disease conditions in animals, mammals (including humans) and plants.

Abstract: Peptidomimetic macrocycles and methods for their preparation and use, as well as amino acid analogs and macrocycle-forming linkers, and kits useful in their production, are provided.

Abstract: Analogues of octreotide, their preparation and use are described.

Abstract: The present invention is directed to novel antifungal glycopeptide compounds and salts thereof produced by a strain of Burkholderia contaminans useful for preventing or treating fungal infection or disease in animals and plants and the bacterial strain that produces the compounds.

Abstract: A method of screening compounds or molecules comprising the steps of: translating a sequence encoding the amino acid sequence comprising SEQ ID No. 29 in a translation system in the presence of a test compound or molecule; and analysing the translation product(s) for the presence of one or more of (a) a peptide comprising the amino acids Pro-Gly at the C terminus and a peptide comprising the amino acid Pro at the N terminus: or (b) a peptide comprising the amino acid sequence of SEQ ID No. 29.

Abstract: A polypeptide comprising a first protein domain, a second protein domain, and a dithiocyclopeptide spacer containing at least one protease cleavage site, wherein the dithiocyclopeptide is exogenous relative to the first or second protein domain, and wherein the first and second protein domains are operably linked by the dithiocyclopeptide. Also disclosed are methods of producing the polypeptide and delivering the protein domains into a cell.

Abstract: An antitumor agent containing, in combination, at least one kind of antitumor agent selected from the group consisting of an antitumor agent that forms a cross-link with DNA and shows an antitumor effect, an antimetabolite antitumor agent and a taxane antitumor agent, and a histone deacetylase inhibitor. According to the present invention, an antitumor agent causing reduced side effects and having a superior antitumor activity can be provided.

Abstract: Good bioavailability of desmopressin can be obtained by means of an orodispersible pharmaceutical dosage form. Preferred dosage forms comprise desmopressin and an open matrix network which is an inert water-soluble or water-dispersible carrier material. Desmopressin formulated in this way is useful for voiding postponement, or the treatment or prevention of incontinence, primary noctural enuresis (PNE), nocturia or central diabetes insipidus. Peptides other than desmopressin can also be formulated in this way.

Abstract: The invention relates to synthetic peptide amides that are ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure: wherein Xaa is a D-amino acid and G is selected from the following three groups: The compounds are useful in the prophylaxis and treatment of pain, pruritis and inflammation associated with a variety of diseases and conditions.

Abstract: The present invention relates to the treatment of protozoal diseases by administering cytotoxic and/or cytostatic compounds, in particular those used in anticancer therapy, to patients. In particular, the invention relates to the use of anticancer agents that can penetrate into the CNS for treatment of late stage African sleeping sickness or cerebral malaria.

Abstract: Methods for separation and recovery of individual cyclic peptides from plant materials, said method comprising the steps of: (a) extracting an oil from a plant material; (b) separating the extracted oil into a non-polar fraction and a polar fraction; (c) separation and recovery of cyclic peptides from the non-polar fraction, and (d) separation and recovery of cyclic peptides from the polar fraction. The methods are suitable for separation and recovery of individual cyclolinopeptides from flax seed oil. Individual cyclolinopeptides are useful for modulation physiological disorders associated with apoptosis. Modified flaxseed oils may be produced by comingling flaxseed oils absent cyclolinopeptides, with at least one cyclolinopeptide separated and recovered with the methods disclosed herein.

Abstract: The invention provides cyclo[{4-(NH2—C2H4—NH—CO—O—)Pro}-Phg-DTrp-Lys-Tyr(4-Benzyl)-Phe], optionally in protected form, or a pharmaceutically acceptable salt or complex thereof, which has interesting pharmaceutical properties.

Abstract: The present invention discloses cell penetrating peptides and conjugates of a cell penetrating peptide and a cargo molecule.

Abstract: Non-native synthetic peptide cyclized by means of a disulphide bridge, characterized by the amino acid sequence (E34P) that follows (SEQ ID No. 1): E-D-E-H-K-G-K-Y-C-R-L-G-N-D-C-R-T-T-E-P-T-T-T-A-T-P-R-G-T-P-T-P-A-P and a complex of non-native synthetic peptides that is intended to induce and characterize the prevention and/or treatment of conditions in mammals, the protective immunity of which depends on the stimulation of Th1 type lymphocytes, and, in particular, on a state of delayed hyperstimulation, containing: —said peptide (E34P), —the following sequence (A16E) of 16 amino acids (SEQ ID No. 2) or derivatives (structural analogues) thereof: A-A-R-C-A-R-C-R-E-G-Y-S-L-T-D-E —the following sequence (A16G) of 16 amino acids (SEQ ID No. 3) or derivatives (structural analogues) thereof: A-A-S-S-T-P-S-P-G-S-G-C-E-V-D-G, —and an adjuvant which preferably induces a cell-mediated response.

Abstract: A protein selected from the amino acid sequence of the region valine Val(91) to glycine Gly(l21) of the mature human tumour necrosis factor, or a portion thereof, with the proviso that the protein comprises at least the amino acid sequence of the region lysine Lys(98) to glutamic acid Glu(116), with the cysteine Cys(101) being replaced by a glycine and an amide bond being formed between the amino group of the side chain of the lysine Lys(98) and the carboxyl group of the side chain of the glutamic acid Glu(116), which activates epithelial ion channels and improves the lung function and which can be used for the manufacture of medicaments for the treatment of diseases associated with the lung function, such as oedemas.

Abstract: Embodiments of this invention include synthetic compounds (NRP analogues) of peptides termed neural regeneration peptides (NRPs). NRP analogues are made by substituting amino acids in the native peptide sequence, modifying amino acids chemically, by replacing amino acids with synthetic moieties, by stabilizing ?-turns, acetylation of terminal glycine residues or by cyclization. NRP analogues can be used to treat a variety of conditions involving degeneration of neural cells, and includes treating disorders of the nervous system, including peripheral neuropathy, multiple sclerosis, diabetic peripheral neuropathy, neurotoxin-induced neurodegeneration, and amyotrophic lateral sclerosis.

Abstract: The present invention relates to novel peptide compounds which are effective in modulating one or more melanocortin receptor types, to the use of the compounds in therapy, to methods of treatment comprising administration of the compounds to patients in need thereof, and to the use of the compounds in the manufacture of medicaments. The compounds of the invention are of particular interest in relation to the treatment of obesity as well as a variety of diseases or conditions associated with obesity.

Abstract: The present invention relates to an amyloid ? peptide analogues comprising an amino acid sequence or a peptidomimetic thereof, wherein the sequence (i) forms a loop, (ii) has at least 66% identity to the amino acid sequence of native A? peptide or a portion thereof, (iii) comprises at least 6 contiguous amino acid residues and (iv) has at least 2 non-contiguous amino acid residues which are covalently linked with each other, oligomers comprising a plurality of said amyloid ? peptide analogues, processes for preparing the amyloid ? peptide analogues or oligomers, compositions comprising the amyloid ? peptide analogues or oligomers, and uses of the amyloid ? peptide analogues or oligomers such as their use for treating or preventing an amyloidosis (e.g. by active immunization), for diagnosing an amyloidosis, and for providing agents that are capable of binding to the amyloid ? peptide analogues or oligomers.

Abstract: Embodiments of the invention are directed to a one-bead-two-compound method for the creation of encoded cyclic peptoid libraries. This scheme is useful for the creation of cyclic peptoid microarrays since only the cyclic peptoid, not the linear encoding molecule, contains an attachment residue and thus can be spotted onto an activated substrate.

Abstract: The invention is directed to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A. The mixtures possess enhanced efficacy and reduced toxicity over the individual isomers and over naturally occurring and other presently known cyclosporines and cyclosporine derivatives. Embodiments of the present invention are directed toward cis and trans-isomers of cyclosporin A analogs referred to as ISATX247, and derivatives thereof. ISATX247 isomers and alkylated, arylated, and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. Stereoselective pathways may utilize a Wittig reaction, or an organometallic reagent comprising inorganic elements such as boron, silicon, titanium, and lithium. The ratio of isomers in a mixture may range from about 10 to 90 percent by weight of the (E)-isomer to about 90 to 10 percent by weight of the (Z)-isomer, based on the total weight of the mixture.

Abstract: The present application relate to cyclic depsipeptides, or derivatives thereof, having the formula (I), and uses thereof, e.g. as inhibitors of kallikrein 7.

Abstract: The invention concerns uranium-chelating peptides as well as their uses for decontaminating soils and water, and for detecting and treating people contaminated by uranium. Said peptides have a helix-loop-helix type structure comprising the sequence of a calmodulin loop including at least one mutation of neutral residues selected from the group consisting of S, T, C, H, Y, N and Q, of one, two or three residues of at least one of the four calmodulin calcium binding sites: site I: residues selected among D20, D22 and D24 residues; site II: residues selected among D56, D58 and N60 residues; site III: residues selected among D93, D95 and N97 residues; site IV: residues selected among D129, D131 and D133 residues; said positions being indicated with reference to the human calmodulin sequence.

Abstract: The present invention relates to polypeptides having a brain-localizing activity, molecules comprising these polypeptides, and pharmaceutical agents that confer brain-localizing activity. The present inventors are the first to reveal amino acid motif sequences involved in brain-localizing activity. Polypeptides that comprise such motif sequences and have brain localizing activity were discovered as follows: DNAs encoding polypeptides comprising random amino acid sequences were synthesized, and incorporated into a phage library. The phage library produced was used to screen for polypeptides having brain-localized activity, which yielded such several polypeptides. These polypeptides comprised common sequences, which lead to the successful discovery of amino acid motif sequences involved in brain-localizing activity.

Abstract: The invention provides methods and compositions for production of a cyclic polymer in a cell free system. In general, the methods of the invention involve ligating first and second recombinant intein domains to a linear synthetic polymer to form a compound containing the structure: D1-X(n)-D2, where D1 is a first catalytic domain of an intein; D2 is a second catalytic domain of an intein; where the second catalytic domain has at its N-terminus a first reactive site for the intein; and X(n) is a polymer of a number n of monomer X, where the polymer N-terminus has a second reactive site for the intein. D1-X(n)-D2 compounds autocatalytically cyclize the X(n) polymer to produce a cyclic polymer. The invention finds use in a variety of drug discovery, clinical and therapeutic applications.

Abstract: The present invention relates to a method of inhibiting or reducing the proliferation of prostate cancer cells, such as androgen independent prostate cancer (AIPC) cells, the method comprising administering to the cells a PLA2 inhibitor. In one embodiment the PLA2 inhibitor is a conformationally constrained molecule derived from a peptide consisting essentially of amino acid residues 70-74 of a human sPLA2-IIA protein, or the equivalent residues in other sPLA2 proteins.

Abstract: Disclosed herein are peptides which include an isoDGR motif and which selectively inhibit ?v?3 integrin. In some embodiments, the isoDGR motif results from the deamidation of an NGR motif.

Abstract: A compound having the general structure R1, R2, R3 and R4 being selected from the group consisting of a hydrogen atom (H) and a C1-C20 alkyl, and R5 being a phenyl radical.

Abstract: The present invention relates to monomeric and multimeric peptidic compounds which have antimicrobial activity, particularly against Gram-positive and Gram-negative bacteria. Further, the present invention refers to compositions comprising said peptidic compounds for medical use, for use as a disinfectant and/or detergent or for use as a preservative.

Abstract: The present invention relates to novel mimetopes of anti-PSMA antibodies and their use for detecting, imaging, staging, treating and monitoring of prostate cancer, and/or metastatis thereof. The present invention also relates to novel pharmaceutical compositions for the treatment of prostate cancer. Furthermore the present invention relates to assay systems and kits for detecting, imaging, staging, treating and monitoring of prostate cancer, and/or metastasis thereof.

Abstract: Embodiments of the present invention relate to a three dimensional matrix of selected, synthetic peptide mimic sequences that are preferentially recognized by auto-antibodies, specifically by autoimmune antibodies, to be detected in patients afflicted with rheumatic arthritis, enabling enhanced sensitivity and specificity in detection of these antibodies in pre-symptomatic patients, in patients showing symptoms as well as patients confirmed positive for rheumatoid arthritis.

Abstract: The subject invention provides advantageous new salts of mu-opiate receptor peptides. These salts have been found to have excellent properties in terms of their activity.

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: A cyclic peptide of the structural formula: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, m and p are as defined. Further provided are compositions for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction, by administration of a cyclic peptide including a C-terminus —OH group. Routes of administration include injection, oral, urethral, vaginal, nasal and mucosal administration.

Abstract: The present invention falls within the field of molecular biology, and in particular it refers to peptides, polypeptides, protein molecules, uses, methods, processes, systems and compositions for minimizing the presence of molecules in a material and/or interfering with effects associated to such molecules. In particular, the present invention can appear in the form of anti-septic shock pharmacological composition and systems of purification from bacterial endotoxins.

Abstract: Peptide nanotube polymers and methods of making such are disclosed. The peptide nanotube polymers comprise of alternating monomers of the first peptide ring and monomers of the second peptide ring covalently bonded to one another via a linker, and can be functionalized. The described peptide nanotube polymers can enjoy the combined properties of healing and toughness, self-reporting, and tunability and actuation.

Abstract: The present invention relates to novel compounds, pharmaceutical compositions comprising the same, use of said compounds for the manufacture of a medicament for treatment of inter alia compromised lactation conditions as well as to a method for treatment of said conditions, wherein said compounds are administered. The compounds are represented by the general formula (I), as further defined in the specification.

Abstract: The invention is related to anti-viral phosphinate compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: The invention relates to method of detecting autoantibodies from patients suffering from rheumatoid arthritis. To this end, according to the invention, at least two peptide units are used of which at least one peptide unit comprises a part not derived from (pro)filaggrin, fibrin, fibrinogen, vimentin, cytokeratin 1 and cytokeratin 9, and which peptide unit comprises the motif XG, and a peptide unit comprising the motif XnonG, wherein X is a citrulline or an analogue thereof, and nonG is an amino acid other than glycine.

Abstract: The present invention is directed to novel non-invasive diagnostic tools/compounds comprising a cyclic peptide wherein the compound binds to a MSH receptor to image and treat cancers, especially, melanoma, including metastatic melanoma in vivo. The present invention represents a clear advance in the art which presently relies on tissue biopsy for diagnoses of these cancers. The novel imaging probes are capable of detecting cancerous melanoma cells, as well as their metastatic spread in tissues. This represents a quantum step forward in the diagnosis and treatment of melanoma, including metastatic melanoma using non-invasive molecular imaging techniques. The novel probes of the present invention will also be useful to initiate therapy for melanoma as well as monitor patients response to chemotherapy treatments and other interventions or therapies used in the treatment of melanoma/metastatic melanoma.

Abstract: The disclosure provides methods of detecting autoantibodies present in the serum of subjects suffering from rheumatoid arthritis. The methods use capture probes and detection probes that can bind to the antifilaggrin autoantibodies or other epitope related autoantibodies. The presence, absence, and/or amount of the autoantibody complex may be detected, wherein the presence of the complex may indicate a positive diagnosis of rheumatoid arthritis.

Abstract: Semi-synthetic glycopeptides having antibacterial activity are described, in particular, the semi-synthetic glycopeptides described herein are made by chemical modification of a glycopeptide (Compound A, Compound B, Compound H or Compound C) or monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in acidic medium to give the amino acid-4 monosaccharide; conversion of the monosaccharide to the amino-sugar derivative; acylation of the amino substituent on the amino acid-4 amino-substituted sugar moiety on these scaffolds with certain acyl groups; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Key reaction is the treatment of properly protected intermediate compound with isocyanate.

Abstract: The invention provides methods and compositions for production of a cyclic polymer in a cell free system. In general, the methods of the invention involve ligating first and second recombinant intein domains to a linear synthetic polymer to form a compound containing the structure: D1-X(n)-D2, where D1 is a first catalytic domain of an intein; D2 is a second catalytic domain of an intein; where the second catalytic domain has at its N-terminus a first reactive site for the intein; and X(n) is a polymer of a number n of monomer X, where the polymer N-terminus has a second reactive site for the intein. D1-X(n)-D2 compounds autocatalytically cyclize the X(n) polymer to produce a cyclic polymer. The invention finds use in a variety of drug discovery, clinical and therapeutic applications.

Abstract: The present invention relates to a new cyclic peptide compound or a salt thereof, which has anti-hepatitis C virus activities based on inhibitory activity against the RNA replication of hepatitis C virus replicon, to a process for preparation thereof comprising a rearrangement reaction under a mild acidic condition and the following amino acid changing reactions etc., to a pharmaceutical composition comprising the same, and to a method for prophylactic and/or therapeutic treatment of hepatitis C in a human being or an animal.

Abstract: The disclosure relates to methods of ameliorating nephrotoxic side effects of immunosuppressive agents whose immunosuppressive activity is mediated via upregulation of TGF-? such as, for example, cyclosporine (CsA). The disclosure provides treatment modalities for use in patients that require immunosuppression, e.g., patients at risk of transplant rejection or having an autoimmune disease. In the methods of the invention, a TGF-? antagonist, e.g., an anti-TGF-? antibody, is administered to a patient treated with an immunosuppressive agent. Such a TGF-? antagonist is administered in a therapeutically effective amount sufficient to alleviate the nephrotoxic effects of the immunosuppressive agent without substantially interfering with immunosuppressive activity of the agent.

Abstract: The present invention provides derivatives of lipopeptide antibiotics that display antimicrobial activity against microorganisms, methods and compounds for synthesizing such antimicrobial derivatives and analogues, and methods of using the compounds in a variety of contexts, including in the treatment and prevention of microbial infections.

Abstract: The present invention provides novel macrocyclic compounds that mimic peptide substrates of the hepatitis C viral protease and inhibit the viral protease, more particularly as inhibitors of the NS3 serine protease from hepatitis C virus. Methods for synthesis of the compounds are also provided. The compounds find utility as antiviral agents directed at hepatitis C. The invention further provides methods of employing such inhibitors, alone or in combination with other therapeutic agents, to treat hepatitis C infection in a subject in need of such treatment.

Abstract: CRF peptide analogs that bind to CRFR1 with an affinity far greater than they bind to CRFR2. Some of these analogs exhibit CRF agonist activity. One exemplary analog that may be made by solid-phase synthesis is: (cyclo 31-34)[Ac-Pro4,D-Phe12,Nle18,21,Glu31,Lys34]-sucker urotensin(4-41).

Abstract: The invention is directed to isomeric mixtures of cyclosporine analogues that are structurally similar to cyclosporine A. The mixtures possess enhanced efficacy and reduced toxicity over the individual isomers and over naturally occurring and other presently known cyclosporines and cyclosporine derivatives. Embodiments of the present invention are directed toward cis and trans-isomers of cyclosporin A analogs referred to as ISATX247, and derivatives thereof. Mixtures of ISATX247 isomers exhibit a combination of enhanced potency and reduced toxicity over the naturally occurring and presently known cyclosporins. ISATX247 isomers and alkylated, arylated, and deuterated derivatives are synthesized by stereoselective pathways where the particular conditions of a reaction determine the degree of stereoselectivity. The ratio of isomers in a mixture may range from about 10 to 90 percent by weight of the (E)-isomer to about 90 to 10 percent by weight of the (Z)-isomer, based on the total weight of the mixture.

Abstract: The present invention concerns methods and compositions of use for treatment of Alzheimer's Disease (AD). In certain embodiments, the methods concern preparation of phage-display single chain antibody libraries and screening against amyloid-beta (A?) protein or peptide. Anti-A? antibodies are selected and sequenced. In certain embodiments, synthetic A? binding peptides are designed and prepared, using portions of the anti-A? antibody sequences. The antibodies and peptides are of use for treatment of AF or for treatment of individuals at risk of developing AD. Compositions comprising anti-A? antibodies or A? binding peptides are also disclosed.

Abstract: The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.