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: Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

Abstract: The present invention relates to dual-targeting cytotoxic compounds of formula (I) and to their preparation. The described compounds are endowed with tumour specific action, incorporating three functional units: a tumour recognition moiety and a tumour selective enzymatic substrate sequence connected together by means of a spacer. These conjugates are designed to guarantee serum stability and, at the same time, the desired action inside the tumour cells as a result of enzymatic cleavability. [(L-D)nE]m-F-D-PI-SI-CT Formula (I).

Abstract: Provided is a cyclic peptide which comprises: (i) a CDK4 peptide region; and (ii) a cell-penetrating region; wherein the CDK4 peptide region comprises the amino acid sequence P1R1x1y1R2P2V (SEQ ID NO: 1), in which P1 and P2 are each proline, R1 and R2 are each arginine and each of x1 and y1 are either a linker or proline, wherein if x1 is a linker then y1 is proline or if x1 is proline then y1 is a linker, or wherein x1 and y1 when taken together form a linker, and wherein V may be present or absent; and wherein the cell-penetrating region is capable of enhancing the uptake of the cyclic peptide or a part thereof into cancer cells and comprises an amphiphilic amino acid sequence; and wherein the cyclic peptide or a part thereof is cytotoxic to and/or inhibiting to the growth of a cancer cell.

Abstract: Compounds are disclosed of general formula (I): wherein A, B, R1 and R2 are as defined in the description, and their use as pharmaceuticals.

Abstract: One aspect of the invention relates to a peptide comprising the amino acid sequence of formula (I), ENPVVHFFK91NIVTP96RTP?(I)? (SEQ?ID?NO:?3) wherein at least one of K91 and P96 is substituted by a natural or unnatural amino acid, wherein said peptide is in linear or cyclic form. Another aspect of the invention relates to a peptide comprising the amino acid sequence of formula (Ia), ENPVVHFFK91NIVT96RTP?(Ia), (SEQ?ID?NO:?4) wherein each of K91 and P96 is substituted by a natural or unnatural amino acid. Another aspect of the invention relates to a peptide comprising the amino acid sequence of formula (Ib), ENPVVHFFK91NIVT96RTP?(Ib) (SEQ?ID?NO:?5) wherein at least one of K91 and P96 is substituted by an amino acid selected from R, E, F and Y.

Abstract: Disclosed are peptides having a cystine knot structural motif and comprising a sequence engineered for specificity against ?IIb?3 integrin, found on platelets, and a method of using the same in anti-thrombotic therapies. The present peptides utilize a cystine knot scaffold derived from modified agouti-related protein or agatoxin, An alternate library screening strategy was used to isolate variants of peptides that selectively bound to ?IIb?3 integrin or to both ?IIb?3 and ?V?3 integrins. Unique consensus sequences were identified within the identified peptides suggesting alternative molecular recognition events that dictate different integrin binding specificities. In addition, the engineered peptides prevented human platelet aggregation in a plasma-based assay and showed high binding affinity for ?IIb?3 integrin.

Abstract: Dye conjugates of template-fixed ?-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 14 ?-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, or Pro or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties, and are useful for cancer therapy; diagnostic imaging; for detection of tumors and other abnormalities; for photoacoustic tumor imaging, detection and therapy; and for sonofluorescence tumor imaging, detection and therapy. The various dyes forming part of these conjugates are useful over the range of 300-1200 nm, the exact range being dependent upon the particular dye. These dye conjugates of ?-hairpin peptidomimetic can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

Abstract: The present invention relates to a method for processing microbiologically produced, non-polar, cyclic oligopeptides comprising the step of a) extracting the entire fermentation broth incident to the microbiological production process using a liquid extractant that contains ether and is immiscible with water, wherein the amount of extractant is sufficient to form a two-phase system together with the total fermentation broth, and novel solvates of cyclosporin A and methyl-t-butyl ether.

Abstract: The present invention relates to an improved process for the large scale synthesis of cyclic heptapeptide using Fmoc solid phase synthesis technique. The described process assembles the peptide on a solid support resin by coupling to one another by peptide bonds to obtain a peptide wherein the coupling of cysteine to the resin employs a combination of solvents to reduce cysteine racemization. The process described relates to the use of C1-C4 alcohols as total substitute to organic nitriles thus making the process cost effective, non-toxic and eco-friendly.

Abstract: The use of a peptide is described as a carrier for the transport of molecules or radioisotopes into cancer cells; also described are modifications of said peptide and their use.

Abstract: Anticancer compounds of general formula I: wherein R1-R11 take permitted meanings for use in the treatment of cancer.

Abstract: The present invention features the use of a complement inhibitor, e.g., a compstatin analog for treating an individual who has suffered a severe injury. In some embodiments, the complement inhibitor may be administered within 24 hours following the injury and optionally also at later time points. The complement inhibitor may, for example, be administered prior to transporting the patient to a health care facility, during transport of the patient to a health care facility, or in the emergency department. Further provided are methods of selecting individuals for such therapy. Further provided are methods of identifying individuals at increased risk of poor outcome following trauma. In certain embodiments the methods comprise determining whether the genotype of the patient includes an allele of a polymorphism in or near a complement-related gene, wherein said allele is associated with risk of poor outcome following trauma.

Abstract: The invention teaches a method for testing a prospective or known immunomodulatory drug for T-cell activation, comprising the step of contacting in-vitro a peripheral blood mononuclear cell (PBMC) culture with a predetermined amount of the prospective or known immunomodulatory drug and observing the PBMC culture for T-cell activation using a readout system, upon contact with the prospective or known immunomodulatory drug, wherein the cell density of a PBMC preculture is adjusted such that cell-cell contact of the PBMC is enabled and wherein the PBMC preculture is cultured for at least 12 h.

Abstract: The invention provides 4-amino-4-oxobutanoyl peptide compounds of Formula I and the pharmaceutically salts and hydrates thereof. The variables R1-R9, R16, R18, R19, n, M, n, M, and Z are defined herein. Certain compounds of Formula I are useful as antiviral agents. Certain 4-amino-4-oxobutanoyl peptide compounds disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. The invention also provides pharmaceutical compositions containing one or more 4-amino-4-oxobutanoyl peptide compounds and one or more pharmaceutically acceptable carriers. Such pharmaceutical compositions may contain 4-amino-4-oxobutanoyl peptide compound as the only active agent or may contain a combination of 4-amino-4-oxobutanoyl peptide containing peptides compound and one or more other pharmaceutically active agents. The invention also provides methods for treating viral infections, including Hepatitis C infections, in mammals.

Abstract: A method for treating disorders involving deregulation of cell proliferation and/or angiogenesis comprising the administration of an effective amount of a multivalent synthetic compound comprising a support on which at least 3 pseudopeptide units are grafted, said compound being of formula (I).

Abstract: The present invention is directed to peptide analogs of chemokine, the pharmaceutically acceptable salts thereof, to methods of using such analogs to treat mammals and to pharmaceutical compositions useful therefor comprising said analogs.

Abstract: Novel lipopeptides, and engineered polypeptides useful in synthesizing lipopeptides are provided. Also provided are methods of making lipopeptides using engineered polypeptides, and methods of using lipopeptides, e.g., as insecticidal and/or antimicrobial agents.

Abstract: The invention relates generally to cyclic peptides and their use in compositions, especially topical, cosmetic and/or personal care compositions, and compositions containing said cyclic peptides.

Abstract: A compound useful as an antifungal agent, particularly a therapeutic agent for deep-seated mycoses, is provided. A fungus Acremonium persicinum was collected, and cyclic compounds were isolated from culture liquids thereof. The present inventors confirmed that the cyclic compounds or salts thereof have a potent antifungal activity and are useful as medicaments, particularly an antifungal agent, and thus the present invention was completed. The cyclic compound and the salt thereof according to the present invention can be used as an agent for preventing or treating mycoses, particularly deep-seated mycoses.

Abstract: The present invention provides novel cyclosporin analogue compounds, pharmaceutical compositions comprising these compounds and methods of using these compounds for the treatment of disorders and diseases, including immune disorders, inflammatory disorders and viral infections.

Abstract: The present invention provides novel cyclosporin analogue compounds, pharmaceutical compositions comprising these compounds and methods of using these compounds for the treatment of disorders and diseases, including immune disorders, inflammatory disorders and viral infections.

Abstract: The present invention provides novel proline substituted cyclosporinanalogue compounds, pharmaceutical compositions comprising these compounds and methods of using these compounds for the treatment of disorders and diseases, including immune disorders, inflammatory disorders and viral infections.

Abstract: Chemically reactive carbocyanine dyes that are intramolecularly crosslinked between the 1-position and 3?-position, their bioconjugates and their uses are described. 1,3?-crosslinked carbocyanines are superior to those of conjugates of spectrally similar 1,1?-crosslinked or non-crosslinked dyes. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: The present invention provides a conjugate that contains a therapeutic moiety linked to a homing peptide or peptidomimetic which selectively homes to vasculature of pre-malignant dysplastic skin and which includes the amino acid sequence SRPRR (SEQ ID NO: 1) or a conservative variant or peptidomimetic thereof. The present invention further provides a conjugate containing a therapeutic moiety linked to a homing peptide or peptidomimetic which selectively homes to vasculature of malignant skin and which includes the amino acid sequence CGKRK (SEQ ID NO: 6) or the amino acid sequence CDTRL (SEQ ID NO: 7), or a conservative variant or peptidomimetic of one of these sequences.

Abstract: The invention relates to novel cyclic compounds which have the ability to modulate the activity of G protein-coupled receptors. The compounds preferably act as antagonists. In preferred embodiments, the invention provides cyclic peptidic and peptidomimetic antagonists of C5a receptors, which are active against C5a receptors on polymorphonuclear leukocytes and macrophages. The compounds of the invention are both potent and selective, and are useful in the treatment of a variety of inflammatory conditions.

Abstract: Described herein are compositions and methods for use in targeted drug delivery using cell receptor binding drug delivery conjugates containing hydrophilic spacer linkers for use in imaging, diagnosing, and/or treating diseases and disease states caused by pathogenic cell populations.

Abstract: The present invention relates to the use of a non-immunosuppressive cyclosporin A derivative for preventing or reducing muscular degeneration in a subject suffering from Limb-Girdle muscular Dystrophy.

Abstract: An isolated peptide comprising an amino acid sequence HWRR as set forth by SEQ ID NO:5, the peptide consists of 4 or 5 amino acids, is provided. Also provided are methods of treating angiogenesis-related pathologies using the peptide of the invention or pharmaceutical compositions comprising same.

Abstract: The present invention relates to colloidal metal nanoparticles conjugated with Kahalalide F, or an analogue thereof, and their use in the treatment of cancer. The invention also relates to a method for increasing the antitumoral activity of Kahalalide F, or an analogue thereof, which comprises conjugating the Kahalalide F, on an analogue thereof, with a colloidal metal nanoparticle.

Abstract: The invention relates to melanocortin receptor-specific cyclic peptides of Formula (I) or a pharmaceutically acceptable salt thereof, where R1, R2, R3, R4a, R4b, R4c, R5, x and y are as defined in the specification. These compounds are particularly useful in the treatments of energy homeostasis and metabolism related (e.g. diabetes), food intake related and/or energy balance and body weight related diseases, disorders and/or conditions, including obesity, overweight and diseases, disorders and/or conditions associated with obesity and/or overweight, such as type 2 diabetes and metabolic syndrome.

Abstract: The present invention relates to the use of peptide compounds for the prevention and/or treatment of a bacterial infection.

Abstract: The present invention relates to diagnostic imaging and in particular to the diagnostic imaging of fibrosis. More particularly, the present invention provides a polypeptides, cyclic polypeptides and pharmaceutical compositions suitable for the non-invasive visualization of fibrosis. The polypeptide of the invention may comprise an amino acid sequence consisting of: X1-X2-M-H-G-L-X7-L-X9-X10-D-E wherein amino acid X1 is R, F or P; amino acid X2 is F or V; amino acid X7 is Q, H or L; amino acid X9 is W or G and amino acid X10 is A or D.

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: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use treating or preventing HCV infections.

Abstract: The present invention relates to a polymyxin derivative wherein R1, R2 and R3 are optional and R1, R2, R3, R5, R8 and R9 are cationic or neutral amino acid residues selected so that the total number of positive charges at physiological pH is at least two but no more than three; and to a combination product comprising at least two such derivatives.

Abstract: The invention provides an immunogenic molecular entity, a supramolecular assembly, and an antibody that can be used to inhibit Gram-positive bacterial quorum sensing, prevent infection or development of a disease condition associated with a Gram-positive bacterial infection. The invention also provides methods of inhibiting Gram-positive bacterial quorum sensing, and methods of preventing infection or development of a disease condition associated with a Gram-positive bacterial infection.

Abstract: The invention relates to cyclic peptides and methods for producing and using them. Provided is amongst others a method for determining whether a compound comprises antibiotic activity, the method comprising providing a cyclic peptide to a bacterium wherein a 23S rRNA in a 5OS ribosomal subunit does not comprises a 2? O-methylation at a nucleotide that corresponds to nucleotide C 1920 in E. coli and determining whether said compound inhibits growth of said first bacterium.

Abstract: Conjugates of a cargo molecule with a transporter molecule are disclosed, where the cargo molecule and the transporter molecule are linked covalently by a releasable linker. The cargo of the conjugate can be a biologically active agent or a reporter molecule. The transporter modulates the transport of the cargo across a biological barrier (e.g., a cell membrane) compared to the transport of the unconjugated cargo. Releasable linkers suitable for rapid and facile conjugation to various types of cargo and transporters are also disclosed, along with methods for using the linkers in the synthesis of conjugates.

Abstract: A compound, or a pharmaceutically acceptable salt or ester thereof, comprises the structure: [(P1-S1j)p-L-(S2q-P2)r]t wherein: P1 and P2, which may be the same or different, are cyclic oligopeptide moieties, at least one of P1 and P2 having the motif B-Arg or B-(Me) Arg within the cyclic moiety, wherein B is a basic amino acid, a derivative thereof, or phenylalanine or a derivative thereof; S1 and S2 are spacer groups, which may be the same or different; L is a linker moiety containing at least two functional groups for attachment of the cyclic oligopeptides or spacer groups; n and q are independently 0 or 1; p and r are independently integers of 1 or more; and t is an integer of 1 or more, provided that, when t, p or r is greater than 1, the cyclic oligopeptide moiety, spacer group and/or the value of j or q may be the same or different between the multiple (P1-S1j) moieties or multiple (S2q-P2) moieties.

Abstract: Semi-synthetic glycopeptides having antibacterial activity are described. Also described are processes of preparing such semi-synthetic glycopeptides by chemical modification of a glycopeptide (Compound A, Compound B, Compound H or Compound C) or the monosaccharide made by hydrolyzing the disaccharide moiety of the amino acid-4 of the parent glycopeptide in mild acidic medium to give the amino acid-4 monosaccharide; protection of the amino groups in the molecule; and conversion of the acid moiety on the macrocyclic ring of these scaffolds to certain substituted amides. Also included are the process of conversion of the amide group in amino acid-3 on these scaffolds to various acylureas, acylamide, acylsulfonamide, acylsulfonylurea derivatives and aminomethylation with substituent containing sulfonamide or acylsulfonamide group on amino acid-7 through Mannich reaction procedures.

Abstract: Methods of forming soft connective tissue compositions such as skin equivalents, compositions made by the methods and their uses.

Abstract: The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone, concurrently or not in the dosage regime of the present invention.

Abstract: The invention concerns a compound of formula (I), wherein Y represents a macrocycle whereof the cycle comprises 9 to 36 atoms, and is functionalized by three amine or COOH functions; Rc represents a group of formula H—Xa—Xb—Xc—Xd—Xe—(Xf)i—, wherein i represents 0 or 1, Xn is in particular selected among lysine, arginine, ornithine residues, Xb is in particular selected among glycine, asparagine, L-proline or D-proline residues, Xc et Xd are in particular selected among tyrosine, phenylalanine or 3-nitrotyrosine residues, Xe et Xf are in particular selected among the following amino acid residues: NH2—(CH2)n—COOH, n ranging from 1 to 10 or NH2—(CH2—CH2—O)m—CH2CH2COOH, m ranging from 3 to 6, provided that one at least of the amino acid residues Xa, Xb, Xc and Xd is different from the corresponding amino acid in the sequence of the natural CD40 143Lys-Gly-Tyr-Tyr146 fragment

Abstract: This invention relates to cyclosporin derivatives of general formula (I): wherein A, B, R1, R2 and X are as defined in the specification, and pharmaceutical compositions prepared from the same, for use in treatment of hepatitis C virus.

Abstract: Disclosed herein are guanidinium containing compounds consisting of a core moiety with a plurality of side chains containing guanidinium groups. Such compounds have enhanced translocation across cellular membranes and epithelial tissues. The compounds may also have a therapeutic or other biologically active moiety attached so that these moieties may be effectively transported into a cell by the guanidinium containing compound.

Abstract: The present invention relates to a compound WS727713, useful as a modulator of melanocortin receptors, and a process for its production by culturing in a culture medium the actinomycetes strain of the genus Pseudonocardia, deposit number FERM BP-7570 and recovering the compound.

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, a process for preparation thereof, a pharmaceutical composition comprising the same, and a method for prophylactic and/or therapeutic treatment of hepatitis C in a human being or an animal.

Abstract: The present invention relates to novel hybrid cyclopeptide compounds embodying pyrrolidine- or piperidine-based amino acid substructures grafted onto a RGD (-Arg-Gly-Asp-) tripeptide sequence and acting as targeting ligands towards integrin receptors, intended, for example, for the treatment of altered angiogenic phenomena or for the preparation of therapeutically and/or diagnostically useful compounds; the invention also concerns a process for the synthesis of said cyclopeptides and biologically active derivatives thereof.

Abstract: The present invention relates to HIV-1 envelope proteins from a donor with non-progressive HIV-1 infection whose serum contains broadly cross-reactive, primary virus neutralizing antibody. The invention also relates to isolated or purified proteins and protein fragments that share certain amino acids at particular positions with the foregoing HIV-1 proteins.