Abstract: The invention relates to a method for enriching phosphopeptides. Said method is characterized in that a carrier is used which carries phosphate groups and/or phosphonate groups on the surface thereof. The phosphate groups and/or phosphonate groups are functionalized with zirconium ions and are bonded to the carrier by means of linker structures which have at least one alkyl chain containing at least 5 C atoms. Also disclosed are corresponding carriers and suitable kits for enriching phosphopeptides.

Abstract: The present invention relates to the crystal structure of the insulin receptor ectodomain, to the nature of its N-linked glycans and to methods of using the crystal and related structural information to screen for and design compounds that interact with or modulate the insulin receptor and/or the closely-related insulin-like growth factor receptors or variants thereof.

Abstract: The invention relates to a method for preserving peptides or proteins over long periods of time. The invention also relates to the use of the preservation method for the transport of labeled peptides or proteins without requiring refrigeration, as well as to a set of tools for implementing said method.

Abstract: Peptides have been identified that bind to oral surfaces such as teeth and gums. Peptide based oral care reagents have been created by couple such peptides to oral care benefit agents such as whiteners.

Abstract: The invention relates to a method for linking two or more molecular substances, by means of adapter segments, which bring about a targeted interaction based upon the affinity of proline-rich amino acid sequences and protein domains of the type WW.

Abstract: A method for selectively orienting molecules on a surface of a solid support. The method includes: (a) attaching a linker molecule to the surface of the solid support, the linker molecule including a head group that is capable of binding to the solid support, and a tail group that is capable of chelating to a metal ion; (b) subsequently treating the solid support with a solution containing the metal ion; (c) attaching a metal ion chelating tag to the molecules to form tagged molecules; and (d) capturing the tagged molecules on the solid support by contacting it with the tagged molecules to form a monolayer of molecules on the surface of the solid support in which a majority of the molecules are held in the same orientation with respect to the surface.

Abstract: The invention relates to low-molecular doxorubicin peptide derivatives containing MMP-2 or MMP-9 divisible peptide sequences and a protein-binding group.

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 disclosure provides compounds and compositions, and methods of using these compounds and compositions, for the targeted delivery of chemotherapeutic agents.

Abstract: The present invention relates to a soluble hydrophobic-core carrier composition comprising (i) a linear polymeric backbone; (ii) a plurality of hydrophilic polymeric protective chains covalently linked and pendant to the polymeric backbone and (iii) at least one hydrophobic moiety covalently linked and pendant to the polymeric backbone. In certain embodiments, the weight ratio of hydrophilic protective chains to hydrophobic moieties in the carrier is at least 15:1. In other embodiments, at least 90% of the residues of the polymeric backbone are coupled to a hydrophilic polymeric protective chain or a hydrophobic moiety. In other embodiments, the composition further comprises (iv) a hydrophobic load molecule dissociably linked to the hydrophobic moiety of the carrier.

Abstract: The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.

Abstract: This invention relates to fluorescent probes for identification of compounds binding to protein kinases, for measurement of the affinity of inhibitors of protein kinases, and determination of the active concentration of protein kinases binding to the probe. Bisubstrate-analog character of the probe enables the simultaneous evaluation of inhibitors targeted to both ATP binding site and/or substrate protein/peptide binding domain of the kinase. High affinity of the probe (Kd=1.0 nM towards cAMP-dependent protein kinase) affords the application of the enzymes at low concentration which leads to the substantial decrease of the consumption of the kinase. Due to the ability of the conjugates of oligo(D-arginine) with a ATP binding site targeted inhibitors of this invention to bind with high affinity to a wide spectrum of (basophilic) kinases, a single Fluorescent probe is applicable for assessment of inhibitory potency of compounds towards a great number of protein kinases.

Abstract: This invention relates to methods of treatment of inflammatory airway disease, and in particular to methods of treatment of asthma and chronic obstructive pulmonary disease. The invention is applicable to both allergic (atopic) and non-allergic (intrinsic) asthma. In one form the method comprises the step of administering an effective amount of a compound which has the ability to inhibit one or more functions of the T cell receptor (TCR) to a subject in need of such treatment, which is preferably a peptide whose sequence is derived from an invariant region of (a) the TCR? transmembrane domain; (b) the TCR? transmembrane domain; (c) the TCR? intracellular domain; or (d) the CD3-?, -?, -?, ? or ? chain.

Abstract: The present invention relates to novel chimeric C3-like Rho antagonists and their use for promoting repair and neuron survival in injured mammalian central and peripheral nervous system and for treating or preventing cancer.

Abstract: The present invention is directed to phenylalanine ammonia-lyase (PAL) variants produced by prokaryotes, wherein such prokaryotic PAL variant has a greater phenylalanine-converting activity and/or a reduced immunogenicity as compared to a wild-type PAL. The invention provides compositions of prokaryotic PAL and biologically active fragments, mutants, variants or analogs thereof, as well as methods for the production, purification, and use of such compositions for therapeutic purposes, including the treatment of cancer.

Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a therapeutic agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two therapeutic agents and one PEG moiety. In alternative embodiments, the therapeutic agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one therapeutic agent. In more preferred embodiments, the therapeutic agent may comprise any peptide or protein of physiologic or therapeutic activity, preferably a cytokine, more preferably interferon-?2b. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

Abstract: The present invention relates generally to methods and carriers for cross-linking or immobilising biomolecules such as polypeptides. In particular, the present invention relates to methods and carriers useful for coupling a polypeptide to a carrier via at least one disulphide bond. The carrier coupled to the biomolecules has applications in the fields of e.g. molecular biology, biochemistry, pharmacology, and medical diagnostic technology.

Abstract: A molecular probe comprises two arsenic atoms and at least one cyanine based moiety. A method of producing a molecular probe includes providing a molecule having a first formula, treating the molecule with HgOAc, and subsequently transmetallizing with AsCl3. The As is liganded to ethanedithiol to produce a probe having a second formula. A method of labeling a peptide includes providing a peptide comprising a tag sequence and contacting the peptide with a biarsenical molecular probe. A complex is formed comprising the tag sequence and the molecular probe. A method of studying a peptide includes providing a mixture containing a peptide comprising a peptide tag sequence, adding a biarsenical probe to the mixture, and monitoring the fluorescence of the mixture.

Abstract: The invention provides populations of molecules that are prepared as, or treated to become, homogeneous for one or more molecular characteristics. In an aspect, the invention relates to molecular weight standards that may be used to determine the molecular weight or apparent molecular weight of uncharacterized molecules, such as proteins and nucleic acids, as well as in other applications. In one aspect, the molecular weight standards are pre-stained.

Abstract: The invention provides for methods for producing water-soluble iron oxide nanoparticles comprising encapsulating the nanoparticles in phospholipids micelles. Also provided are methods for conjugating the inventive nanoparticles via functionalized phospholipids to a target molecule, such as an antibody. The invention further provides methods for using the nanoparticle-antibody conjugate of the invention as a contrast agent to image specific cells or proteins in a subject using fluorescent and magnetic imaging techniques.

Abstract: Disclosed are compositions and methods for prenylation of polymers such as peptides.

Abstract: Methods are described for phototransferring a compound from a first surface to a second surface. Compounds are described with photocleavable linkers. Compounds attached to a first surface through a photocleavable linker are put in proximity (or contact) with a second surface, and then phototransferred to the second surface upon exposure to electromagnetic radiation. Illuminating the compound with radiation photocleaves the compound from the first surface and transfers the compound to the second surface.

Abstract: The present invention relates to methods and intermediates for chemical synthesis of polypeptides and proteins, and more particularly to methods and intermediates for chemically ligating a peptide fragment containing N-terminal ?-methyl-cysteine (SEQ ID NO: 1) with another peptide fragment having C-terminal thioester to generate a ?-amino-thioester intermediate that spontaneously rearranges to form an amide bond. The invention also relates to methods of synthesizing ?-methyl-cysteine (SEQ ID NO: 1) and its protected forms. Furthermore, the invention relates to converting a ?-methyl-thiazolidine residue to a ?-methyl-cysteine (SEQ ID NO: 1) residue of polypeptides and proteins.

Abstract: A method for destroying harmful cells is provided, applicable in treating proliferative diseases. The cells are destroyed by a combined treatment with a chemiluminescent agent and with a ligand-photosensitizer conjugate. The chemiluminescent agent emits light on reacting with oxygen species present in situ, the conjugate binds to the cell through its ligand and is activated by the emitted light, thereby destroying the cell. The method is demonstrated on a conjugate of transferrin-hematoporphyrin, which destroys cancerous cells in the presence of luminol.

Abstract: A method for PEGylating growth hormone, said method comprising reacting growth hormone with an amine comprising nucleophile which further comprises a first functional group in the presence og TGase to form a transaminated growth hormone, followed by a reaction of said transaminated growth hormone with a PEG which has been functionalised with a second functional group, wherein said first and second functional groups are selected so that they react to form a covalent bond.

Abstract: Organosilicon-functional phase transfer catalysts (PTCs) and methods for transferring immiscible molecules into a silicon-functional phase employing an organosilicon-functional PTC are provided.

Abstract: The present invention relates to methods for the formation of inter-molecular disulphide bonds, including (poly)peptides/proteins, nucleic acids, vectors, host cells and bacteriophages used in these methods. Furthermore the invention relates to the use of this method for the improved display of (poly)peptides/proteins on the surface of bacteriophage particles.

Abstract: The present invention relates to molecular probes of the formula (I) {L1-R1-L}n-A-CO—NH—R2-L2??(I) as defined herein that allow for the observation of the catalytic activity of a selected cathepsin in in vitro assays, in cells or in multicellular organisms, a method for their preparation and the use thereof.

Abstract: Disclosed is a method for indirectly coupling a small molecule ligand to a molecule to be labelled with the ligand, the method comprising the step of: contacting a scaffold molecule, to which is attached at least one small molecule ligand, with the molecule to be labelled, the scaffold molecule having at least one group which is reactive towards a receiver moiety present or formed in situ on the molecule to be labelled, so as to forma bond between the scaffold molecule and the molecule to be labelled, thereby indirectly coupling the small molecule ligand to the molecule to be labelled.

Abstract: Method for increasing half-life of therapeutic agents in plasma and novel polypeptide derivatives.

Abstract: Novel stable, concentrated, biologically active and ready-to-use lipid-comprising drug delivery complexes and methods for their production are described. The biological activity of the complexes produced are comparable to the formulations prepared according to the prior art admixture method and upon purification, the complexes produced by the method of this invention are 50 to 500 fold more concentrated than the complexes formed by admixture. The method described herein provides for the large scale production of lipid-comprising drug delivery systems useful for gene therapy and other applications.

Abstract: A method for preparing a site-specific peptide probe, wherein the peptide is specific to a receptor, includes modifying a marker to include a tether molecule and covalently binding the tether molecule to the peptide. The present invention also provides a labeled probe, comprising a peptide specific for a receptor and a marker. The marker is modified to include a tether molecule capable of covalently binding to the peptide. The peptide is typically derived from a bacteriophage or is a synthetic analog or derivative of the peptide. The receptor will typically be found on a surface of a bacterial cell. The method and probe of the invention are suitable for a rapid assay for a bacteria in a complex mixture.

Abstract: Disclosed is a series of somatostatin-dopamine chimeric analogs which retain both somatostatin and dopamine activity in vivo.

Abstract: The present invention provides functionalized molecules comprising a covalently linked autosilification moiety; and methods for making and using the functionalized molecules. The present invention provides nucleic acids comprising nucleotide sequence encoding polypeptides comprising an autosilification moiety. The present invention further provides silica matrices comprising a subject functionalized molecule, as well as systems and kits comprising the silica matrices. The subject functionalized molecules find use in various applications, which are also provided.

Abstract: The invention relates to portable albumin binders, which are useful for improving the pharmacokinetic properties of diagnostic or therapeutic agents, in particular increasing the blood circulations time and/or the tissue penetration capacity of such agents.

Abstract: Compounds having two reactive functional groups are described that can be used to provide a connector group between a substrate and an amine-containing material. The first reactive functional group can be used to provide attachment to a surface of a substrate. The second reactive functional group is a N-sulfonylaminocarbonyl group that can be reacted with an amine-containing material, particularly a primary aliphatic amine, to form a carbonylimino-containing connector group. The invention also provides articles and methods for immobilizing amine-containing materials to a substrate.

Abstract: A process for preparing an enantiomerically enriched amino alcohol or derivatives thereof having the structure: wherein C* is a chiral carbon atom and R1 and R2 are independently selected from hydrogen, alkyl, alkoxy, aryl and a peptide chain, wherein said process includes the steps of: (a) providing an amino acid having the structure of Formula I: (b) protecting the amino group of the Formula I amino acid with a carbobenzoxy(Cbz) N-protecting group by reacting the amino acid with benzyl chloroformate in the presence of a base; (c) forming a carboxylic acid alkyl ester of the Cbz N-protected Formula I amino acid by reacting the amino acid with a C1-12 alcohol; and (d) reducing the Cbz N-protected amino acid ester with a borohydride reducing agent in an organic solvent or mixture of organic solvents to form a Cbz N-protected amino-alcohol

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: 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 invention relates to methods for making a peptide standard for mass spectrometry said method comprising (a) identifying endopeptidase cleavage sites in a parent polypeptide sequence of interest; (b) selecting peptide sequences from said parent polypeptide which are defined by endopeptidase cleavage sites of step (a); (c) adding a C-terminal extension to each selected sequence; wherein if the endopeptidase cleavage site is C-terminal to its recognition sequence then the C-terminal extension comprises 1 to 6 amino acids, wherein if the endopeptidase cleavage site is N-terminal to its recognition sequence then the C-terminal extension comprises said recognition sequence, wherein if the endopeptidase cleavage site is within its recognition sequence then the C-terminal extension comprises the remainder of said recognition sequence C-terminal to the cleavage site; and (d) synthesising a peptide having the extended amino acid sequence of step (c).

Abstract: A novel compound, 2?/3?-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2? and 3? regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2?-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2?/3?-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2?/3?-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2?/3?-O-acetyl-ADP-ribose are also provided.

Abstract: Methods of modulating interfacial characteristics in a self-assembled, force-transmitting peptide network at a fluid-fluid interface are disclosed. The methods involve exposing a peptide capable of participating in a self-assembled, force-transmitting peptide network, either before or after it interacts with other peptides to form the peptide network to a stimulus that alters the chemical and/or physical properties of the peptide. Use of such methods in applications such as emulsions and foams are also disclosed.

Abstract: The present invention relates to a method of cleaving a polypeptide at one or more phosphorylated residues. Said cleavage is induced by irradiation and is dependent on the presence of uranyl. The method is useful for analysis of phosphoproteoms and also for protein purification. The method also relates to a method of protein purification, wherein the phosphorylated protein is immobilized on a column said immobilization being dependent on uranyl.

Abstract: In one aspect, the present invention provides a functionalized monodisperse polylysine comprising a linear monodisperse polylysine chain comprising constituent lysine monomer residues containing appended C4-C24 polyethylene glycol groups and at least one appended fluorescent dye moiety is provided.

Abstract: The invention generally features compositions and methods that are useful for modulating blood vessel formation, as well as methods that provide for the systematic and efficient identification of angiogenesis modulators. As described in more detail below, a systematic computational methodology based on bioinformatics was used to identify novel peptide modulators of angiogenesis that have been characterized in vitro and/or in vivo.

Abstract: The invention relates to a method for the preparation of a stabilized cross-linked oligomer of amyloid beta using a near-zero length bifunctional cross-linking agent for use as an immunogen for the generation of antibodies for the treatment of Alzheimer's Disease and other conditions related to abnormal amyloid beta aggregation. A preferred bifunctional cross-linking agent is 1,5-difluoro-2,4-dinitrobenzene (DFDNB).

Abstract: This disclosure provides the construction, expression, and selection of the mutated genes that encode novel Trp cage polypeptides with desirable binding properties, as well as the novel Trp cage polypeptides themselves. The substances or targets bound by these novel Trp cage polypeptides may be but need not be proteins or polypeptides. Targets may include other biological or synthetic macromolecules as well as other organic and inorganic substances. Further, targets may also include a single or multiple cell or tissue types. The present invention achieves genetic variants of Trp cage-encoding nucleic acids through controlled random mutagenesis of the nucleic acids yielding a mixture of Trp cage polypeptides that are capable of binding targets.

Abstract: A method of making a synthetic glycopeptide, by addition of a synthetic oligosaccharide oxazoline to a GlcNAc-containing peptide precursor in the presence of an enzyme selected from among Endo-A and Endo-M. In a specific implementation, the method is utilized to synthesize a trivalent V3-domain glycopeptide including three V3-domain glycopeptides on a scaffold, wherein the three V3-domain glycopeptides are arranged to mimic the V3 domain presentation in trimeric gp120. Such trivalent V3-domain glycopeptides can be utilized in a vaccine for the treatment or prevention of HIV-1 infection.

Abstract: The present invention is directed to a method for the generation of binding proteins derived from the protein super-family of ubiquitin like proteins with modifications in their alpha helical region as well as to a protein obtainable by said method. Furthermore, the invention provides the use of a protein for the specific recognition, binding and neutralization of a predescribed target molecule, for the detection, quantitative determination, separation and/or for the isolation of a corresponding binding partner and the use of a protein of the invention, for diagnosis, prophylaxis and treatment of diseases in which the corresponding binding partner is directly or indirectly involved.

Abstract: The invention is based on the discovery that the presence of a discordant helix in a protein or peptide is predictive of that protein or peptide's ability to form amyloid. The invention includes methods for detecting discordant helices and methods of screening for compounds that stabilize the ?-helix of a discordant helix-containing polypeptide. Compounds discovered using these methods are useful for treating or preventing disorders in which amyloid is produced. Such disorders include Alzheimer's disease and prion-associated disorders.