Abstract: The present invention discloses latent thioester functionalities attached to the C-terminus of a first polypeptide, or a first fragment thereof having a Cys residue at its N-terminus, and a process using this functionality for the preparation of polypeptide thioesters, in particular of ubiquitin thioesters, this process comprising preparing a polypeptide or a fragment thereof, being attached to a latent thioester functionality, which can then be ligated with a second polypeptide fragment, followed by selective activation of the latent thioester functionality group, to provide the requested polypeptide thioester. There are also provided the polypeptides obtained by this method, specific unnatural amino acids useful to be incorporated within the polypeptide thioesters, and kits for preparing them.

Abstract: A method is disclosed for carrying out peptide synthesis comprising deprotecting an Fmoc-protected amino acid with piperazine while applying microwave irradiation to the deprotection reaction.

Abstract: A particulate body having a hollow particle and a surface polymer disposed on the outside of the hollow particle and suitable for use in solid phase synthesis, especially production of peptides and oligonucleotides. The particulate body may be used as a chromatography stationary phase column and the buoyancy of the body allows the column to be packed efficiently from the bottom reducing the risk of damage to the stationary phase. The buoyancy of the particulate body may also allow species for example a catalyst to be suspended in a liquid phase to allow reactions, for example hydrolysis of vegetable oil and esterification to produce biodiesel to be carried out with a reduced risk of catalyst loss from a reaction zone.

Abstract: The invention mainly relates to a method for manufacturing a polypeptide of formula: X1—X?—X2??(III) X1 and X2 each representing a peptide fragment, and X? representing an amino acid residue comprising a thiol function, said method comprising at least one step of ligation reaction between a polypeptide of formula: X1—N(CH2CH2SH)2??(I) and a polypeptide of formula: H—X?—X2.??(II) The invention also relates to the polypeptides of formula (I) themselves and the method for obtaining them, as well as resin supports suitable for obtaining them.

Abstract: The invention provides high-yield protein dimerization methods using highly reactive bis-thioimidates that may be used in the manufacture of a highly potent anti-cancer peptide dimers.

Abstract: The invention relates to the production of ovoproducts containing bioactive peptides from the egg white subjected to enzymatic treatment. Said peptides have an inhibiting activity of the angiotensin converting enzyme (ACE inhibiting activity) in vitro and/or anti-hypertensive activity in rats and/or antioxidant activity. Said ovoproducts, complete hydrolyzates, the fractions thereof with low molecular weight or their constituent peptides could be used as therapeutic substances with ACE inhibiting activity and/or anti-hypertensive activity and/or anti-oxidant activity, either as functional food products, food additives or ingredients or pharmaceutical products for the treatment and/or prevention of hypertension in all its forms in humans or animals and for the treatment and/or prevention of any disorder associated with hypertension in humans or animals.

Abstract: The invention discloses methods for sequential protein isolation and purification from a biological sample by affinity chromatography. Affinity chromatography is conducted using ligands or ligand support complexes that selectively and specifically bind to proteins in the biological sample. The ligands or ligand support complexes were contacted sequentially in a predetermined order with the biological sample to allow each ligand or ligand-support complex to sequentially bind a protein from the biological sample.

Abstract: The invention relates to a functionalised solid support for the synthesis of compounds comprising at least one ?-oxoaldehyde function, to a process for preparing it and to its applications, in particular for the preparation of a library of organic compounds, of a diagnostic reagent, of a microtitration plate and of a biochip, such as a DNA chip. The present invention also relates to a process for the synthesis of organic compounds comprising at least one ?-oxoaldehyde function and to the ?-oxoaldehyde peptides obtained using this process.

Abstract: The present invention relates to the synthesis of depsipeptides on solid phase support. Said depsipeptides are then implicated in a solution phase O—N acyl shift enabling to obtain the corresponding peptide alcohols.

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: 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 solid phase peptide synthesis method is disclosed. The method includes the steps of deprotecting an amino group in its protected form that is protected with a protecting group containing a Michael acceptor site composed of an ?,?-unsaturated sulfone in a solvent selected from the group consisting of water, alcohol, and mixtures of water and alcohol; washing the deprotected acid in a solvent selected from the group consisting of water, alcohol, and mixtures of water and alcohol; coupling the deprotected acid to a resin-based peptide or a resin-based amino acid in a solvent selected from the group consisting of water, alcohol, and mixtures of water and alcohol; and washing the coupled composition in a solvent selected from the group consisting of water, alcohol, and mixtures of water and alcohol.

Abstract: A composition and method is described for intracellular delivery of fullerene containing peptides. The composition and method involve fullerene-substituted phenylalanine as part of a peptide based delivery system. The presence of a fullerene-substituted amino acid in a peptide is found to alter the intracellular transport properties of the peptide.

Abstract: Disclosed herein are novel peptide amphiphile molecules and compositions discovered to possess improved solubility in aqueous buffers which, in turn, facilitates purification required for pharmaceutical applications, particularly for in vivo administration to human patients. In addition, gels of such peptide amphiphile compositions are shown herein to possess unexpectedly superior gelation kinetics and rheological properties, including an increased mechanical stiffness, which better mimics the mechanical properties of natural central nervous system tissues.

Abstract: The present invention is directed to alkanal derivatives of water-soluble polymers such as poly(ethylene glycol), their corresponding hydrates and acetals, and to methods for preparing and using such polymer alkanals. The polymer alkanals of the invention are prepared in high purity and exhibit storage stability.

Abstract: The present invention provides a process for producing a peptide thioester compound. The process involves: (A) forming a peptide by a solid-phase synthesis method using a resin modified with a linker represented by the formula (1) as a solid phase: wherein R1 represents C1-4 alkyl group, R2 represents hydrogen atom or C1-4 alkoxy group, and n represents an integer of 1 to 4; (B) cleaving a bond between the solid phase and the peptide with at least one acid selected from dilute hydrochloric acid, dilute sulfuric acid, formic acid, and acetic acid to produce a peptide having a carboxyl group at the C-terminus; and (C) reacting a thiol compound with the peptide at ?100 to 0° C. in the presence of a condensing agent in a solvent.

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: A method of forming a solid-phase support, the method including the steps of providing a substrate having a reaction vessel, dispensing a particle in the reaction vessel, and permanently bonding the particle in the substrate within the reaction vessel. The particle may include a microbead. The particle may include controlled pore glass. A method of synthesis is also disclosed that includes including the steps of providing a solid-phase support including a particle embedded to the substrate adjacent a surface of substrate, the particle being functionalized to covalently attach an intermediate compound of a synthetic reaction, dispensing a liquid including a reagent to the solid-phase support to effect the synthetic reaction, and removing the liquid from the solid-phase support by centrifugation, whereby the intermediate compound remains attached to the substrate by the particle.

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: According to the present invention, there is provided a process for synthesis of a first compound selected from peptides, oligonucleotides, and peptide nucleic acids, which comprises synthesis of the first compound linked to a soluble support, wherein the soluble support is degraded following the synthesis so that it can be separated from the first compound.

Abstract: Nanoparticles can include a core linked to a polymerizable moiety that can be polymerized, cross-linked or cured. The polymerizable nanoparticles can be included in a composition for a polymerization, cross-linking or curing reaction in an amount and disposition sufficient for inhibiting or preventing volume shrinkage during polymerization, cross-linking or curing reaction. Also, the nanoparticles can be included with monomers, dendrimers, oligomers or polymers in the compositions that can be reacted to form a polymerized, cross-linked or cured product.

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

Abstract: A novel compound of formula I is devised.

Abstract: An object of the present invention is to provide a method for synthesizing a peptide thioester by using a compound that can be easily obtained within a relatively short time under conditions in which a side reaction is unlikely to occur. In the present invention, a thioester bond is formed by elongating a peptide chain using N-alkyl cysteine as the C-terminal amino acid according to the Fmoc method, carrying out deprotection, and then causing the peptide bond to undergo N—S transfer to the thiol group of N-alkyl cysteine under weak acidic conditions.

Abstract: Methods and compositions for generating mixtures of product molecules from an initial chemical array are provided. In the subject methods, a chemical array of surface immobilized first moieties is subjected to cleavage conditions such that a composition of solution phase first moieties is produced. The resultant composition of solution phase first moieties is then contacted with one or more reactants to produce a mixture of product molecules that are different from the first moieties. Also provided are the arrays employed in the subject methods and kits for practicing the subject methods.

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: A peptide containing a poly-Gly sequence, such as bivalirudin, can be prepared in a purified form in which low amounts of GIy deletion or GIy addition byproducts are present. A protected poly-Gly-containing peptide is attached to a resin using Fmoc-Gly-GIy-OH units for assembly of the poly-Gly segment. The protected peptide is then cleaved from the resin with an acidic composition to produce an unprotected or semi-protected crude peptide, which can then be isolated from acidic composition.

Abstract: The present invention relates to a pipecolic linker and its use as a solid-phase linker in organic synthesis. Said pipecolic solid-phase linker may be used for coupling functional groups chosen between primary amines, secondary amines, aromatic amines, alcohols, phenols and thiols. In particular, said pipecolic solid-phase linker may be used for peptide or pseudopeptide synthesis, such as the reverse N to C peptide synthesis or the retro-inverso peptide synthesis, or for the synthesis of small organic molecules.

Abstract: The invention provides a cyclomonomer having actin-binding activity. The cyclomonomer is of utility for the study of the molecular biology of actin polymerization. The cyclomonomer is also useful for the study of and treatment of the toxic effects of Amanita sp. poisoning.

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: 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.

Abstract: The present invention provides a method for identifying inhibitors of protein kinases. Methods are also provided for inhibiting protein kinase activity. Specific non-peptide protein tyrosine kinase inhibitors are provided. The protein kinases produced using the method of the present invention may be used to treat a number of conditions in patients, including cancer, psoriasis, atherosclerosis, or immune system activity.

Abstract: The present invention relates to an improved process for the preparation of N6-(aminoiminomethyl)-N2-(3-mercapto-1-oxopropyl)-L-lysylglycyl-L-?-aspartyl-L-tryptophyl-L-prolyl-L-cysteinamide, cyclic(1?6)-disulfide of formula (1), which involves assembling a peptide chain comprising of six amino acids and a thioalkyl carboxylic acid in a required sequence on a solid support to obtain a peptide bound resin of formula (2), capping the free amino groups after each coupling, cleaving Dde group in the peptide of formula (2) from the solid support to obtain peptide-solid support of formula (3), guanylating the peptide of formula (3) at ?-lysine-NH2 in an organic solvent to obtain peptide-solid support of formula (4), cleaving and deprotecting all groups in the peptide of formula (4) from the solid support to obtain peptide-amide formula (5), oxidizing the SH-peptide of formula (5) with an appropriate oxidizing agent to obtain the crude peptide-amide of formula (1) and purifying the crude peptide-amide of formula (1)

Abstract: A method and system for organic polymer synthesis utilizing flow through reaction vessels. A chemical plug is introduced selectively into reaction vessels that are inactive. Reactions continue in other reaction vessels. The chemical plug may be removed after reactions in the other reaction vessels have been completed. All reaction vessels are under a pressure differential which, with the use of the chemical plug, remains uniform.

Abstract: The present invention relates to a controlled metathesis-driven polymerisation process which is particularly useful for the synthesis of biological polymers such as peptides and polymers. The invention also provides metathesisable supports, groups and linkers for use in the process.

Abstract: The present invention is directed to alkanal derivatives of water-soluble polymers such as poly(ethylene glycol), their corresponding hydrates and acetals, and to methods for preparing and using such polymer alkanals. The polymer alkanals of the invention are prepared in high purity and exhibit storage stability.

Abstract: The present invention provides a solid support for Fmoc-solid phase synthesis of peptides. In particular, the solid supports of the invention may be utilized to produce peptide acids.

Abstract: The invention provides methods of chemically synthesizing chimeric proteins comprising at least a portion of an immunoglobulin constant region and a biologically active molecule.

Abstract: Functionalized supports and methods for solid phase synthesis. Preferably, the functionalized support is azlactone-functionalized.

Abstract: The peptides and derivative metapeptides based upon natural antimicrobial peptides have potent and broad spectrum activity against pathogens exhibiting multiple antibiotic resistance. Specific peptides can also potentiate the antimicrobial functions of leukocytes, such as neutrophils. In addition, they exhibit lower inherent mammalian cell toxicities than conventional antimicrobial peptides, and overcome problems of toxicity, immunogenicity, and shortness of duration of effectiveness due to biodegradation, retaining activity in plasma and serum. The peptides and derivative metapeptides exhibit rapid microbicidal activities in vitro, can be used to potentiate conventional antimicrobial agents, to potentiate other antimicrobial peptides, and are active against many organisms that exhibit resistance to multiple antibiotics currently in existence.

Abstract: Compounds that modulate natural ? amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a ? amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a ? amyloid peptide, preferably a retro-inverso isomer of A?17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an acetate group, an alkyl amide group, an aryl amide group or a hydroxy group.

Abstract: The present invention provides a process for preparing an immobilized peptide derivative of formula (Vb): comprising reacting a functionalized solid support comprising Sub-L wherein Sub is a solid support and L is a cleavable linker, with H—[NH—A—C(O)]—O(tBu), then reacting the immobilized product with compound of the formula RHN—A—C(O)OH, wherein the RHN—A—C(O) group is the residue of a N-protected ?-amino acid, in the presence of a coupling agent, to yield an immobilized peptide derivative of the formula (Vb).

Abstract: The present invention provides a method and compositions for synthesizing an oligopeptide or polypeptide by convergent assembly of a plurality of pairs of oligopeptides in chemical ligation reactions. An important aspect of the present invention is an oligopeptide having a C-terminal disulfide-protected carboxythioester group that can be deprotected to spontaneously generate a free C-terminal thioester moiety. This allows a single precursor to participate in a succession of chemical ligation reactions, thereby making the convergent synthesis approach possible. The present invention is useful in methods for chemical synthesis of oligopeptides, polypeptides and proteins, and improves the efficiency of native chemical ligation reactions, particularly where four or more peptide fragments are used to assemble an oligopeptide, polypeptide or protein product.

Abstract: A new method of anchoring a growing peptide chain during chemical synthesis to a solid-phase support is devised. Novel amino acid derivatives and peptide derivatives, both unbonded and bonded to a solid-phase support, are also provided.

Abstract: Novel iminium-type coupling agents containing proton acceptors in their iminium moiety, which can be used beneficially as coupling agents in various chemical polypeptide and/or polynucleotide syntheses, and are particularly useful as yield enhancing and racemization suppressing coupling agents for use in peptide syntheses, are disclosed. Further disclosed are a process of preparing such iminium-type coupling agents and their use in the preparation of polypeptides and/or polynucleotides.

Abstract: The present invention relates to an automated polymer synthesis apparatus for synthesizing a polymer chain onto a solid substrates by sequentially adding polymer building blocks as well as to a method for synthesizing polymers on solid substrates by sequentially reacting polymer building blocks with reactive groups. The invention further relates to a biochip comprising a solid substrate with reactive groups where biomolecules are attached to and the remaining reactive groups are transformed into chemically inert species.

Abstract: The inventors disclose here a novel, facile approach to the synthesis of acetonide-protected catechol-containing compounds having at least one amine group. In specific embodiments, the invention provides novel methods of synthesizing 3,4-dihydroxyphenylalanine (H-DOPA(acetonide)-OH (6)), Fmoc-protected H-DOPA(acetonide)-OH (Fmoc-DOPA(acetonide)-OH (7)), Fmoc-protected dopamine (Fmoc-dopamine(acetonide) (10)), TFA-protected dopamine (TFA-dopamine(acetonide) (13)) and acetonide-protected 4-(2-aminoethyl)benzene-1,2-diol (acetonide-protected dopamine (14)).

Abstract: A process is provided for the solid-phase synthesis of a peptide amide which comprises attaching an ?-nitrogen protected C?-carboxamide amino acid to a solid support by its side chain, removing the ?-nitrogen protecting group, assembling a peptide chain on said ?-nitrogen and then cleaving the assembled peptide amide from the solid support. Novel amino acid analogues, peptide amides and solid-phase supports are also provided.

Abstract: The instant invention comprises a process for the solid phase synthesis of directed epitope peptide mixtures useful in the treatment and diagnosis of protein conformational disorders, such process defined by a set of rules regarding the identity and the frequency of occurrence of amino acids that substitute a base or native amino acid of a known epitope. The resulting composition is a mixture of related peptides for therapeutic use. The invention also pertains to the process of generating antibodies using the directed epitope peptide mixtures as the antigens, and antibodies generated by such process, useful in the treatment and diagnostics of the said protein conformational disorder.

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.