Abstract: The present invention encompasses a novel S. aureus bioconjugate vaccine. More generally, the invention is directed to Gram-positive and other bioconjugate vaccines containing a protein carrier, at least one polysaccharide such as a capsular Gram-positive polysaccharide, and, optionally, an adjuvant or pharmaceutically acceptable carrier. The instant invention also includes methods of producing Gram-positive and other bioconjugate vaccines. An N-glycosylated protein is also provided that contains one or more polysaccharides such as Gram-positive polysaccharides. The invention is additionally directed to engineered prokaryotic organisms comprising nucleotide sequences encoding a glycosyltransferase of a first prokaryotic organism and a glycosyltransferase of a second prokaryotic organism. The invention further includes plasmids and prokaryotic cells transformed with plasmids encoding polysaccharides and enzymes which produce an N-glycosylated protein and/or bioconjugate vaccine.

Abstract: The present invention relates to a method of labelling biological molecules with 18F, via attachment to fluorine to a macrocyclic metal complex of a non-radioactive metal, where the metal complex is conjugated to the biological molecule. Also provided are pharmaceutical compositions, kits and methods of in vivo imaging.

Abstract: This invention is directed to methods, kits, non-nucleotide probes as well as other compositions pertaining to the suppression of binding of detectable nucleic acid probes to undesired nucleotide sequences of genomic nucleic acid in assays designed to determine target genomic nucleic acid.

Abstract: The present invention relates to a method for preparing carbohydrate T cell epitope conjugates of formula (I): M(T-B)n(I) wherein M, T, B and n are as defined in claim 1.

Abstract: The present invention relates to methods and compositions pertaining to conjugates comprising a nucleic acid oligomer conjugated to a glucosamine or a derivative thereof which are useful for inhibiting the transcription of target nucleic acids. The conjugates of the invention exhibit advantageous bioavailability and readily penetrate cell membranes which make them useful for inhibiting translation of target mRNA in vivo.

Abstract: The present disclosure describes environmentally responsive polypeptides capable of displaying stimuli-triggered conformational changes in a reversible or irreversible manner that may be accompanied by aggregation. Polypeptides include a number of repeated motifs and may be elastomeric or non-elastomeric. The polypeptides may be used to deliver therapeutics to a biological site and to develop bioactive polypeptides that are environmentally responsive.

Abstract: The present invention provides conjugates between peptides and PEG moieties. The conjugates are linked via an intact glycosyl linking group that is interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from both glycosylated and unglycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto either an amino acid or glycosyl residue on the peptide. Also provided are pharmaceutical formulations including the conjugates. Methods for preparing the conjugates are also within the scope of the invention.

Abstract: The present invention is related to a nucleic acid molecule capable of binding to human C5a, wherein the nucleic acid molecule comprises a central stretch of nucleotides, wherein the central stretch of nucleotides comprises a nucleotide sequence of 5? AUGn1GGUGKUn2n3RGGGHUGUKGGGn4Gn5CGACGCA 3? [SEQ ID NO: 61], wherein n1 is U or dU, n2 is G or dG, n3 is A or dA, n4 is U or dU, n5 is U or dU and G, A, U, C, H, K, and R are ribonucleotides, and dU, dG and dA are 2?-deoxyribonucleotides.

Abstract: Vancomycin B Hydrochloride Crystalline Form 1, compositions containing it and methods of prevention or treatment of bacterial infections using it are disclosed.

Abstract: The invention provides, in one aspect, peptides and a complex comprising one of the peptides and a cargo molecule, wherein the peptide and the cargo molecule are coupled by non-covalently. The peptides of the invention were found to facilitate the delivery of siRNA molecules into cells and to function in siRNA mediated silencing of cellular targets.

Abstract: The invention relates to relatively short peptides (termed ?-conotoxins herein), about 10-30 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.

Abstract: The invention relates to methods for effecting qualitative and quantitative changes in the functional moieties expressed at the surface of cells and multi-cellular structures, and functional lipid constructs for use in such methods. In particular, the invention relates to functional lipid constructs and their use in diagnostic and therapeutic applications, including serodiagnosis, where the functional moiety is a carbohydrate, peptide, chemically reactive group, conjugator or fluorophore.

Abstract: Methods for building peptide chains containing sulfonyl modified amines at the N-terminus, or, within amino acid side chains, of a growing peptide in a solid-phase peptide synthesis are described. Further, compositions having a sulfonyl modified amine attached to the N-terminus, or within an amino acid side chain, of a polypeptide containing three or more amino acid residues are described.

Abstract: The present invention provides nanoparticles and compositions comprising such nanoparticles, as well as methods for intracellular delivery of peptides, and methods of producing nanoparticles and related products. The nanoparticles comprise a core comprising a metal and/or a semiconductor atom; and a corona comprising a plurality of ligands covalently linked to the core, wherein at least a first ligand of said plurality comprises a carbohydrate moiety that is covalently linked to the core via a first linker, and wherein at least a second ligand of said plurality comprises a peptide of choice that is covalently linked to the core via a second linker. The second linker comprises a peptide portion and a non-peptide portion, wherein said peptide portion of said second linker comprises the sequence X1X2Z1, wherein: X1 is an amino acid selected from A and G; X2 is an amino acid selected from A and G; and Z1 is an amino acid selected from Y and F.

Abstract: A delivery system for introducing a cargo molecule into cytosol of a living cell can include: a first membrane binding element linked to an endosomal compartment disrupting element through a first linker having one or more anionic moieties; and a second membrane binding element linked to an exogenous cargo molecule through a second linker having one or more anionic moieties, the second linker having a region that is selectively cleavable, wherein the first and second membrane binding elements both induce endocytosis into an early/recycling endosome and the endosomal compartment disrupting element destabilizes the early/recycling endosome such that the exogenous cargo molecule is released from the second membrane binding element and into the cytosol of the living cell.

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: Peptide helices stabilized by backbone cyclization which are capable of inhibiting dimerization of the Chemokine (C-C motif) receptor 2 (CCR2), as well as pharmaceutical compositions including such backbone cyclized peptide helices. Use of pharmaceutical compositions and peptide helices in treatment of Multiple Sclerosis (MS) and other diseases associated with CCR2 activation.

Abstract: The present invention relates to new methods and reagents for coupling molecules by a Click reaction using a heterogeneous catalyst system. Further, the present invention refers to novel devices for carrying out Click reactions.

Abstract: The peptides described herein can function as carrier peptides. These peptides can associate with (e.g., non-covalently bind) biologically active molecules or imaging agents to transport the biologically active molecules or imaging across the blood-brain barrier. In some cases, such transport may increase the effectiveness of the biological molecules or imaging agents.

Abstract: Disclosed are an anti-influenza nucleic acid, peptide nucleic acid and preparations thereof. The nucleic acid of the invention consists of any one or several of SEQ ID NOs: 1-12, and any one or several of SEQ ID NOs: 13-24. The peptide nucleic acid of the invention consists of any one or several of SEQ ID NOs: 25-36, and any one or several of SEQ ID NOs: 37-48. The peptide nucleic acid preparation of the invention has effective ingredients of said peptide nucleic acids. The anti-influenza peptide nucleic acid of the invention is of high bioavailability and stable physical and chemical properties with no toxic or side effect and no drug tolerance. With low cost, the drugs can inhibit influenza virus replication and have good anti-virus effect.

Abstract: Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.

Abstract: An isolated polypeptide comprising an amino acid sequence selected from amino acids 506-582 of SV2A, wherein position 573 is N and is glycosylated, or amino acids 449-525 of SV2B, wherein position 516 is N and is glycosylated. The present invention also provides an antibody that binds specifically to the polypeptide, an isolated nucleic acid comprising a polynucleotide that encodes the polypeptide; a method for reducing BoNT/E toxicity in an animal; a method for identifying an agent that blocks or inhibits binding between BoNT/E and an SV2A or SV2B protein; a method for monitoring synaptic vesicle endo- or exocytosis, a method for specifically delivering a chemical entity to a cell which has a specific receptor to a BoNT toxin.

Abstract: A vaccine preparation for treating cancer includes a complex of a hydrophobized polysaccharide and at least one synthetic long peptide derived from a tumor-specific antigenic protein and/or a pathogen-derived antigenic protein. The at least one synthetic long peptide contains at least one CD8+ cytotoxic T-cell recognition epitope and at least one CD4+ helper T-cell recognition epitope. The complex is simultaneously administered to the patient with at least one immunopotentiating agent.

Abstract: This invention provides novel reagents for cyanating polysaccharides in aqueous or part aqueous solutions so that they may be covalently linked to proteins either directly or through a spacer. These reagents include 1-cyano-4-pyrrolidinopyridinium tetrafluoroborate (CPPT), 1-cyano-imidazole (1-CI), 1-cyanobenzotriazole (1-CBT), or 2-cyanopyridazine-3(2H)one (2-CPO), or a functional derivative or modification thereof. The examples illustrate the use of these reagents with a variety of polysaccharides and proteins showing that the methods are generally applicable.

Abstract: The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor.

Abstract: The present invention provides a neutralized glucomannan scaffold capable of promoting cell growth and suitable for three-dimensional tissue culture and engineering. The present invention also provides methods for making and degrading the neutralized glucomannan scaffold. The present invention further provides a method of growing cells on a neutralized glucomannan scaffold.

Abstract: The present invention discloses a matrix comprising a modified polysaccharide consisting of repeating disaccharide units whereby in at least 11% of the disaccharide units one primary alcohol group is oxidized into a carboxylic acid group.

Abstract: Immunogenic peptides from tumor associated stromal cell antigens, including combinations of such peptides, are disclosed herein. In some examples the peptides are useful for methods of eliciting an immune response. In additional examples the peptides are useful for methods of treating cancer. Methods for decreasing vascularization of a tumor using a Protein Delta Homolog 1 (DLK1) protein or a nucleic acid encoding the protein are also disclosed.

Abstract: The invention relates to a bonding product suitable as a carrier for medicinal substances and to the compound derived therefrom that carries medicinal substances. The invention further relates to a process and device for preparing such bonding products and compounds. Further, the invention relates to a pharmaceutical composition containing such bonding products and compounds, and to the use thereof for preparing an infusible medicament for treating a disease.

Abstract: It is an object of the present invention to provide improved pharmacological properties to molecules which bind to a target with low affinity (hereinafter referred to as a “ligand moiety”) through linkage of such molecules to a metal binding moiety, thereby generating a combination molecule commonly referred to as a “metallodrug” or “metallotherapeutic.” The metal binding domain of metallodrugs typically catalyzes oxido-reductase chemistry or acts as a Lewis-Acid catalyst, resulting in modification of proteins and nucleic acids that are in close proximity due to binding of the ligand moiety to its target.

Abstract: Disclosed are glycopeptides that are substituted with one or more substituents each comprising one or more phosphono groups; and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.

Abstract: The invention relates to an immunogenic HIV-1 gp120 mini V3 loop, which is a truncated version of the full-length gp120 V3 loop useful for crystallization with antibodies that recognize carbohydrate moieties. The invention also relates to the structure of a broadly neutralizing antibody as a complex with a glycosylated gp120 outer domain, as determined by crystallographic techniques, and the confirmation that a glycosylated gp120 outer domain has a functional relevant conformation, as well as the determination of key residues on a glycosylated gp120 outer domain, and uses thereof and compounds and compositions therefrom. Furthermore, the invention also relates to other peptides and mimetic peptides, which bind to broadly neutralizing antibodies.

Abstract: This invention pertains to the field of hyaluronic acid-binding synthetic peptidoglycans and methods of forming and using the same.

Abstract: Implantable modular hydrogels to aid in salivary gland restoration and associated methods are provided. In one embodiment, the present disclosure provides for a hydrogel network comprising: a hyaluronic acid macromer crosslinked with a multiblock copolymer.

Abstract: The present invention provides compositions and methods useful for delivering agents to target cells or tissues, for example nerve cells and other cells in the central nervous system. The compositions and methods are useful for delivering agents across the blood-brain barrier. The present invention also provides methods of using the compositions provided by the present invention to deliver agents, for example therapeutic agents for the treatment of neurologically related disorders.

Abstract: The present invention is directed to an inventive polymeric carrier molecule according to generic formula (I) and variations thereof, which allows for efficient transfection of nucleic acids into cells in vivo and in vitro, a polymeric carrier cargo complex formed by a nucleic acid and the inventive polymeric carrier molecule, but also to methods of preparation of this inventive polymeric carrier molecule and of the inventive polymeric carrier cargo complex. The present invention also provides methods of application and use of this inventive polymeric carrier molecule and the inventive polymeric carrier cargo complex as a medicament, for the treatment of various diseases, and in the preparation of a pharmaceutical composition for the treatment of such diseases.

Abstract: The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Abstract: The subject invention pertains to methods of making crosslinked protein-carbohydrate conjugates (CPCCs) and uncrosslinked protein-carbohydrate conjugates (PCCs) that are heat, pH and salt stable. Methods of stabilizing CPCCs and PCCs are also provided. The PCCs and CPCCs formed according to the methods disclosed herein are useful in the food industry and for loading with substances of interest.

Abstract: A peptide clearing agent is provided for clearance of a conjugate of an enzyme and a binding molecule which binds specifically at a target location from a non-target location in a subject. The peptide clearing agent binds the active site of the enzyme. The peptide also binds to the asialoglycoprotein receptor expressed by hepatic cells to facilitate clearance through the liver. The peptide may be glycosylated to facilitate clearance through the liver by binding to hepatic cells expressing an asialoglycoprotein receptor. Typically, the peptide prevents or inhibits enzyme activity upon binding to the enzyme and is not substantially modified by the enzyme activity. The peptide may be based upon the dipeptide amino-naphthoic acid (ANA)-glutamate (GIu) and may comprise the amino acid sequence serine (Ser)-Alanine (Ala)-amino-naphthoic acid (ANA)-glutamate (GIu). In such cases, the enzyme of interest is typically CPG2.

Abstract: The present invention relates to methods and compositions for the treatment of diseases, including cancer, infectious diseases and autoimmune diseases. The present invention also relates to methods and compositions for improving immune function. More particularly, the present invention relates to multifunctional molecules that are capable of being delivered to cells of interest for the treatment of diseases and for the improvement in immune function.

Abstract: This disclosure provides extracellular matrix-binding synthetic peptidoglycans comprised of one or more synthetic peptides conjugated to a glycan and methods of their use.

Abstract: Compositions and methods are provided for the treatment or prevention of RSV disease by modulating RSV infection and immunity. In particular, amino acid sequences in the RSV G glycoprotein, containing the chemokine motif defined as C-X-X-X-C (or CX3C), are identified that are essential in causing RSV infection and disease. The chemokine motif is biologically active and participates in virus binding to and infection of susceptible cells. The prevention or treatment of RSV infection is achieved by interfering with the motif, such as by administering a vaccine in which the motif is altered or by administration or induction of blocking molecules that inhibit the biological activity of the motif.

Abstract: The present invention relates to a compound of formula I: wherein x is in the range of from about 1 to about 2. The invention also relates to pharmaceutical compositions containing such compounds; processes for preparing such compounds; and methods of using such compounds to, for example, treat a bacterial infection.

Abstract: Described herein are isolated polypeptides each containing one or more receptor-binding sites of toxin A (tcdA) of Clostridium difficile (Cd), nucleic acids encoding the polypeptides, and methods of using the polypeptides and nucleic acids.

Abstract: The present invention provides novel n-alkenyl glycosides and glycoconjugates, n-alkyl glycoamino acids, and methods for the synthesis thereof. In another aspect, the present invention provides novel clustered glycopeptides and methods for the synthesis thereof. In still another aspect, the present invention provides methods for the treatment of cancer, preferably for the prevention of recurrence of cancer, and methods for inducing antibodies in a subject, comprising administering to a subject in need, an effective amount of any of the inventive glycoconjugates as disclosed herein.

Abstract: The invention concerns a novel antimicrobial peptide (AMP) polymer conjugate comprising at least one AMP, typically colistin, and a dextrin polymer wherein said dextrin polymer has a molecular weight between 5,000-60,000 g/mol and is modified by the additions of pendant groups which increase the stability of the conjugate and so delays its degradation thereby slowing the rate at which the AMP is released.

Abstract: Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of autoimmune disease, inflammatory disease, or cancer. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.

Abstract: Conjugated molecules are prepared that comprise a predetermined number of oligo conjugation components. The conjugated molecules also may comprise one or more detectable labels. Preparation of these molecules can be implemented according to an asymmetric or a symmetric conjugation strategy.

Abstract: The present invention relates to methods for searching and identifying absent and rare peptide sequences from public databases and their uses in the treatment of pathological diseases. One embodiment of the present invention provides a method that includes: a) storing, in a memory or storage of a computing device, a set of at least one peptide sequence of fixed length; b) searching, by the computing device, for a peptide sequence from the set within at least one database having naturally-occurring amino acid sequences; and c) classifying, by the number of appearance in the database, the peptide sequence.

Abstract: Methods and materials are provided for the production of glycosylated peptides that exhibit high affinity and specificity for delta opioid receptors. The methods and materials of the present invention may be used for treatment of conditions involving pain, such as acute pain and nociceptic pain, neuralgia and myalgia.