Abstract: An instrument and associated method are disclosed for the accelerated synthesis of peptides by the solid phase method. The instrument includes a microwave cavity, a microwave source in communication with the cavity, a column in the cavity formed of a material that is transparent to microwave radiation, a solid phase peptide support resin in the column, respective filters for maintaining the solid phase support resin in the column, a first passageway for adding starting compositions to the column, a second passageway for removing compositions from the column, and a third passageway for circulating compositions from the column into the third passageway and back to the column.

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one aromatic amine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one alkylated amine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: The present invention pertains to methods for identifying a HLA-A*2402-restricted cryptic epitope in an antigen, and for increasing its immunogenicity, in order to obtain HLA-A*2402-restricted epitopes able to trigger an immune response against HLA-A*2402-restricted cryptic epitopes. Isolated peptides consisting of cryptic or optimized HLA-A*2402-restricted epitopes are provided.

Abstract: Neural regeneration peptide consisting of a sequence comprised in the sequence of REGRRAAPGRAGG(SEQ ID NO:1).

Abstract: The present invention is directed to compounds, compositions, and methods useful for delivering polynucleotides or other cell-impermeable molecules to mammalian cells. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery vehicles. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.

Abstract: The disclosed invention pertains to improved oligonucleotide manufacturing methods, including novel support compositions that are optionally labeled, their methods of preparation and use. The compositions and methods are particularly well suited for high throughput oligonucleotide manufacturing in that the automated support recognition facilitates loading of the wells with the proper supports. In addition, the labeled supports can be used to confirm that each well of a multi-well plate, such as a 96 or 384 well plate, was properly loaded.

Abstract: There are provided a soluble CD14 antigen which is a novel in vivo protein useful as a marker for diagnosing sepsis and has the following characteristic features 1) to 3): 1) a molecular weight of 13±2 kDa when measured by SDS-PAGE under non-reducing conditions; 2) an amino acid sequence in which the amino acid sequence of SEQ ID NO:1 is present on its N terminal; and 3) ability to specifically bind to an antibody prepared by using a peptide comprising 16 amino acid residues described in SEQ ID NO:2 for the antigen; and a recombinant soluble CD14 fragment.

Abstract: According to the present invention, there is provided a range of new conotoxin derivatives and methods for synthesizing these analogues and other intramolecular dicarba bridge-containing peptides, including dicarba-disulfide bridge-containing peptides.

Abstract: A system and method for identifying a botulinum neurotoxin inhibitor employing a botulinum neurotoxin substrate complex having a peptide substrate, preferably SNAP-25, a reporter domain on one side of said peptide substrate and an immobilization domain on the opposite side of said peptide substrate. The botulinum neurotoxin inhibitor is identified by its ability to decrease the relative amount of cleaved complex, detected through measuring a decrease in complex bound to a solid support. The method of the present invention also utilizes novel cells that express a botulinum neurotoxin substrate complex. The methods of the present invention are adapted for cell based screening to monitor the catalytic activity of a BoNT in living cells and to identify molecules that inhibit the catalytic activity of a BoNT in living cells.

Abstract: A honeycomb body is disclosed having cells extending along a common direction, a first plurality of the cells being open at both ends of the body and a second plurality of the cells being closed at one or both ends of the body, the second plurality of cells arranged in one or more groups of cells cooperating to define one or more fluid passages extending through the body at least in part perpendicularly to the common direction, wherein, in a plane perpendicular to the common direction, the ratio of the area of cells of the first plurality to the area of cells of the second plurality varies along the length of at least one of the one or more fluid passages.

Abstract: Some embodiments relate to analogs of peptides corresponding to class I MHC-restricted T cell epitopes and methods for their generation. These analogs can contain amino acid substitutions at residues that directly interact with MHC molecules, and can confer improved, modified or useful immunologic properties. Additionally classes of analogs, in which the various substitutions comprise the non-standard residues norleucine and/or norvaline, are disclosed.

Abstract: The invention at hand describes a method for the cyclization of peptides and proteins in which linear thioesters serve as substrates. The cyclization is catalyzed by thioesterase domains of NRPS or PKS cyclases. The substrates according to the present invention are composed of one linear peptide on which a charge-stabilized aromatic, heteroaromatic or araliphatic leaving group is bound. These substrates lead to higher yields and reaction rates than linear peptides able to be cyclized with methods known so far and, furthermore, allow the cyclization of such peptides which were previously not able to be cyclized.

Abstract: An instrument and method for accelerating the solid phase synthesis of peptides are disclosed. The method includes the steps of deprotecting a protected first amino acid linked to a solid phase resin by admixing the protected linked acid with a deprotecting solution in a microwave transparent vessel while irradiating the admixed acid and solution with microwaves, activating a second amino acid, coupling the second amino acid to the first acid while irradiating the composition in the same vessel with microwaves, and cleaving the linked peptide from the solid phase resin by admixing the linked peptide with a cleaving composition in the same vessel while irradiating the composition with microwaves.

Abstract: Methods of making copolymers are described.

Abstract: The present invention relates to prodrugs of vascular disrupting agents comprising a vascular disrupting agent (VDA) associated with a MMP proteolytic cleavage site and to the use of such prodrugs in the targeted treatment of cancer.

Abstract: The present invention relates to novel intermediates of formula VII, or an acid addition salt or a solvate thereof, wherein R1 is —(CO)NH2, —CH2NH2 or —CN; R2=R3=H or R2 and R3 together form a cyclic boronate or borate ester; X is a helping group selected from the group consisting of i) a five or six membered heterocyclic aromatic ring and derivatives thereof comprising at least one N-atom being a part of an imine-group, wherein said N-atom forms the point of connection to the cyclohexapeptide ring, and ii) tetrazolyl and derivatives thereof for which a nitrogen atom forms the point of connection to the cyclohexapeptide ring, and a process for the preparation of caspofungin utilizing said intermediates.

Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: The present invention provides antimicrobial peptides and analogs thereof that are cytostatic or cytotoxic toward at least one gram-negative bacterium of the genus Acinetobacter including laboratory or clinical isolates of A. baumannii with low or non-detectable cytotoxicity against mammalian cells. Optionally, the antimicrobial peptides and analogs thereof are also cytotoxic or cytostatic against other unrelated bacteria such as Staphylococcus aureus.

Abstract: A peptide which can adopt a 310-helical conformation in which the side chains of two amino acid residues in the peptide backbone are linked by a group comprising an aromatic 5-membered ring.

Abstract: This invention provides cross-linked glycopeptide—cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.

Abstract: A process comprising substitution of an acceptor molecule comprising a group —XC(O)— wherein X is O, S, or NR8, where R8 is C1-6 alkyl, C6-12 aryl or hydrogen, with a nucleophile, wherein the acceptor molecule is cyclised such that said nucleophilic substitution at —XC(O)— occurs without racemisation, is provided. This process has particular application for the production of a peptide by extension from the activated carboxy-terminus of an acyl amino acid residue without epimerisation.

Abstract: A polypeptide or multimeric polypeptide construct having the ability to bind to cMet or a complex comprising cMet and HGF, and methods for use are disclosed.

Abstract: A method for the manufacture of at least one sorbent having at least two different groups, which are capable of binding, for the selective binding of a substrate, characterized in that it comprises the steps (i) to (ii): (i) determining at least two groups capable of binding a sorbent from a synthetic or natural first substrate, (ii) respectively applying at least two different groups capable of binding a second synthetic or natural substrate to one respective carrier, thereby forming at least one sorbent, whereby the groups are the same groups of step (i) or are groups that are complementary thereto, and the second substrate of step (ii) is the same or different from the first substrate according to step (i), and whereby the groups are determined such that the contributions of the Gibbs energies of the individual groups to the non-covalent bond with the second substrate yield a negative value of the Gibbs energy ?G, such that a binding strengthening occurs that results in an improved separation selectivity

Abstract: Water-soluble thioester and selenoester compounds, their generators, as well as methods for making and using the same, are provided. The subject thioester and selenoester compounds are characterized by including an amino acid synthon having a C-terminal group bonded to a water-soluble polymer through a thioester or selenoester linkage. Solid phase resins and protocols for generating the subject compounds are also provided. The subject water soluble thioester and selenoester compounds and generators find use in a variety of different applications, including thioester or selenoester mediated chemical ligation reactions.

Abstract: According to the present invention, there is provided a process for the preparation of a first compound selected from peptides, oligonucleotides and peptide nucleic acids. The process comprises synthesising the first compound and then separating the first compound formed in step (i) from a second compound, which is a reaction by-product of the synthesis of the first compound and/or an excess of a reagent used for the synthesis of a first compound by a process of diafiltration. The membrane used for the diafiltration process is stable in organic solvents and provides a rejection for the first compound which is greater than the rejection for the second compound.

Abstract: The present invention refers to methods for selectively recognizing a base pair in a DNA sequence by a polypeptide, to modified polypeptides which specifically recognize one or more base pairs in a DNA sequence and, to DNA which is modified so that it can be specifically recognized by a polypeptide and to uses of the polypeptide and DNA in specific DNA targeting as well as to methods of modulating expression of target genes in a cell.

Abstract: The invention relates to peptide derivatives (peptides and pseudo-peptides) and use thereof as vectors for molecules of interest. The invention also relates to conjugates containing a peptide derivative of the invention bound to a molecule of interest. The peptides and prodrug conjugates of the invention can be used to vectorise molecules of pharmaceutical or diagnostic interest, such as, for example, therapeutic molecules, imaging or diagnostic agents, or molecular probes, across cell membranes, and notably to promote their transport across the blood-brain barrier (BBB).

Abstract: Embodiments of this disclosure, among others, encompass methods for generating alkenes under mild thermolytic conditions that can provide almost total conversion of a precursor compound to an alkene without isomerization or the need to chromatographically purify the final product By selectively blocking the amino and carboxy groups of the de?vatized amino acid, the methods of the disclosure provide for the synthesis of a peptide having the vinylglycine moiety at either the carboxy or the amino terminus of the peptide The mild conditions for the thermolytic removal of an o-NO2-phenyl substituted aryl group ensure that there is minimal if any damage to thermally sensitive conjugates such as a peptide bearing the vinylglycine The methods of the present disclosure have practical applications for the preparation of unsaturated compounds under mild, thermolytic conditions.

Abstract: One aspect of the invention relates to novel complexes of technetium (Tc) with various heteroaromatic ligands, e.g., pyridyl and imidazolyl ligands, and their use in radiopharmaceuticals for a variety of clinical diagnostic and therapeutic applications. Another aspect of the invention relates to novel pyridyl ligands that form a portion of the aforementioned complexes. Methods for the preparation of the technetium complexes are also described. Another aspect of the invention relates to novel pyridyl ligands based on derivatized lysine, alanine and bis-amino acids for conjugation to small peptides by solid phase synthetic methods. Additionally, the invention relates to methods for imaging regions of a mammal using the complexes of the invention.

Abstract: The invention provides methods for preparing a peptide as an immunogen to generate an antibody specific for the deglycosylated form of a glycopolypeptide by preparing a peptide that includes an N-linked glycosylation site of said glycopolypeptide and identifying a peptide sequence that includes said glycosylated site and preparing said peptide wherein N of said site is converted to D.

Abstract: The present invention provides materials and methods that make liquid crystal phases accessible with relatively short ?-peptides in aqueous solvents.

Abstract: The present invention provides a composition and a method for cleaving a peptide from a solid support resin. Hydrochloric acid in an organic water miscible solvent is used to cleave the peptide-resin attachment. Optionally, trifluoroethanol or hexafluoroisopropanol may be added to the cleavage composition to improve results. When using the present cleavage composition, an evaporation or other step to remove carboxylic byproducts is not necessary following the cleavage reaction. After the resin is filtered out of the cleavage mixture, the peptide may be immediately precipitated with water.

Abstract: Non-natural amino acids and polypeptides with non-natural amino acids are disclosed. Further, polypeptides with non-natural amino acids that are subject to post-translational modification are disclosed. Additionally, methods of making, purifying, and using non-natural amino acids and polypeptides with non-natural amino acids are disclosed. The non-natural amino acids, by themselves or as part of a polypeptide, can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Uses for the non-natural amino acids and polypeptides with non-natural amino acids include diagnostic, therapeutic, and various biotechnology uses.

Abstract: The invention relates to a process for the preparation of at least one solid phase bound peptide. PNA or a chimera.

Abstract: The invention involves a synthetic peptide derived from HIV-1 virus gp41 having sequence where X615 is F or G, a method of preparing the synthetic peptide, a composition and a kit containing the synthetic peptide, and use of the synthetic peptide in immunoassays for the detection of infections caused by HIV-1 viruses.

Abstract: This invention pertains to the surprising discovery that salicylanilides, e.g., niclosamide and/or niclosamide analogues can be reacted with a therapeutically active peptide to produce a modified peptide complex that shows increased resistance to proteolysis and that shows higher bioactivity when orally administered than the unmodified peptide.

Abstract: The invention provides methods and compositions useful for identifying polypeptides with desired characteristics in vitro.

Abstract: The present invention provides methods for reducing or inhibiting angiogenesis in a tissue, by contacting ?5?1 integrin in the tissue with an agent that interferes with specific binding of the ?5?1 integrin to a ligand expressed in the tissue; and methods of identifying angiogenesis in a tissue, by contacting the tissue with an agent that specifically binds ?5?1 integrin, and detecting specific binding of the agent to ?5?1 integrin associated with a blood vessel in the tissue. Also provided are methods of diagnosing a pathological condition characterized by angiogenesis in a tissue in an individual.

Abstract: The present invention provides novel 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. In various embodiments, the peptidomimetic macrocycles are of Formula I: The linker L includes a triazole moiety. Peptidomimetic macrocycles according to the invention may exhibit increased ?-helical or beta sheet structure in aqueous solution compared to a corresponding non-macrocyclic polypeptide.

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: The present invention provides a method for producing a peptide, characterized in that it comprises converting an —SH group of a peptide comprising an amino acid residue having the —SH group to an —OH group, wherein said method comprises the following steps (a) to (c): (a) allowing an —SH group in a peptide to react with a methylating agent to convert the —SH group to an —SMe group; (b) allowing the —SMe group obtained in the step (a) to react with a cyanizing agent to produce a reaction intermediate; and (c) converting the reaction intermediate obtained in the step (b) to a peptide comprising an amino acid residue having an —OH group under more basic conditions than the conditions in the step (b).

Abstract: A simple, efficient apparatus and method for separating layers of immiscible or partially miscible liquids useful in methods of high-throughput combinatorial organic synthesis or parallel extraction of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis or purification (extraction). In a preferred embodiment, an apparatus and method for separating layers of immiscible or partially miscible liquids compatible with microtiter plate type array(s) of reaction vessels is disclosed. Another application of centrifugation based liquid removal was found for washing the plates in biological assays or synthesis on modified substrates.

Abstract: Biomedical devices with antimicrobial coatings are provided. One or more surfaces of the device are coated with a cationic peptide, cationic proteins, or mixtures thereof to impart antimicrobial properties to the surface.

Abstract: Methods and compositions for the generation of polypeptides having varied material properties are disclosed herein. Methods include means for initiating the polymerization of aminoacid-N-carboxyanhydride (NCA) monomer by combining the monomer with an amido-containing metallacycle, for making self assembling amphiphilic block copolypeptides and related protocols for adding oligo(ethyleneglycol) functionalized aminoacid-N-carboxyanhydrides (NCAs) to polyaminoacid chains. Additional methods include means of adding an end group to the carboxy terminus of a polyaminoacid chain by reacting an alloc-protected amino acid amide with a transition metal-donor ligand complex to forming an amido-amidate metallacycle for use in further polymerization reactions. Novel compositions for use in peptide synthesis and design including five and six membered amido-containing metallacycles and block copolypeptides are also disclosed.

Abstract: Ring-constrained amino acid surrogates of formula I: where R1, R2, R3, R4, R5, R6a, R6b, R7, and y are as defined in the specification, methods for synthesizing ring-constrained amino acid surrogates of formula I, methods of use of ring-constrained amino acid surrogates of formula I, including use in linear or cyclic compounds which include a plurality of amino acid residues and one or more ring-constrained amino acid surrogates of formula I and linear or cyclic compounds which include a plurality of amino acid residues and one or more ring-constrained amino acid surrogates of formula I.

Abstract: Materials and Methods related to gene targeting (e.g., gene targeting with transcription activator-like effector nucleases; “TALENS”) are provided.

Abstract: Disclosed is a method of making ?-polypeptides. The method includes polymerizing ?-lactam-containing monomers in the presence of a base initiator and a co-initiator which is not a metal-containing molecule to yield the product ?-polypeptides. Specifically disclosed are methods wherein the base initiator is potassium t-butoxide, lithium bis(trimethylsilyl)amide (LiN(TMS)2), potassium bis(trimethyl-silyl)amide, and sodium ethoxide, and the reaction is carried out in a solvent such as chloroform, dichloromethane, dimethylsulfoxide, or tetrahydrofuran.

Abstract: Disclosed is a process for preparing a compound of formula (I) by protecting the secondary amide nitrogen atom in the compound of formula (III) to obtain (IV) wherein PGN is a suitable nitrogen protecting group, ring-closing the compound of formula (IV) by cyclizing it in the presence of a suitable catalyst in a suitable organic solvent to obtain (V), and then deprotecting the resulting compound of formula (V) to obtain (I), as outlined in the following scheme. The compounds of formula (I) are active agents for the treatment of hepatitis C viral (HCV) infections or are intermediates useful for the preparation of anti-HCV agents.

Abstract: The present application provides novel human genes C1958V1 or C1958V2 whose expression is markedly elevated in pancreatic cancers compared to corresponding non-cancerous tissues. The genes and polypeptides encoded by the genes can be used, for example, in the diagnosis of pancreatic cancer, and as target molecules for developing drugs against the disease.

Abstract: An instrument and process for accelerating the solid phase synthesis of peptides is disclosed. The method includes the steps of deprotecting a protected first amino acid linked to a solid phase resin by admixing the protected linked acid with a deprotecting solution in a microwave transparent vessel while irradiating the admixed acid and solution with microwaves, then activating a second amino acid by adding the second acid and an activating solution to the same vessel while irradiating the vessel with microwaves, then coupling the second amino acid to the first acid while irradiating the composition in the same vessel with microwaves, and cleaving the linked peptide from the solid phase resin by admixing the linked peptide with a cleaving composition in the same vessel while irradiating the composition with microwaves.