Abstract: Peptide conjugates in which cytocidal and cytostatic agents, such as polyamine analogs or naphthoquinones, are conjugated to a polypeptide recognized and cleaved by enzymes such as prostate-specific antigen (PSA) and cathepsin B are provided, as well as compositions comprising these conjugates. Methods of using these conjugates in the treatment of prostate diseases are also provided.

Abstract: The solvent accessible reduced carbon atoms in a molecule of interest are labeled with heavy hydrogen. The carbon atoms are labeled under anaerobic, aqueous conditions by exposing the molecule of interest to a hydrogen atom abstractor in the presence of a heavy hydrogen source and a heavy hydrogen donor. If the hydrogen atom abstractor is hydroxyl radical, an electron scavenger source is provided. Optionally, an internal reference is provided to facilitate experimental reproducibility.

Abstract: Modified proteins are represented by the formula R-L-R′, wherein R and R′ are peptides or pseudopeptides linked to one another by linkage L. Linkage L may be either a thiol ester pseudopeptide backbone linkage or a selenol ester pseudopeptide backbone linkage.

Abstract: Disclosed herein are aggregating amyloid A&bgr; peptides which are covalently bonded (for example, at a cysteine amino acid residue) to a fluorescent label, and methods for their use.

Abstract: A reagent having the general formula of General Formula I: wherein group Z comprises a spacer selected from an aliphatic chain up to about 6 carbon equivalents in length, an unbranched aliphatic chain of from about 6 to 18 carbon equivalents in length with at least one of an intermediate amide and a disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the reagent with a biologically active species; and wherein group Q is one of nothing at all, an amide, a methyl amide, a methylene, an ether, a thioether, a methyl ether, and a methyl thioether moiety. Also, a conjugate, a bioconjugate and a method of conjugating.

Abstract: This invention provides a combinatorial fluorescence energy transfer tag which comprises a plurality of fluorescent molecules, comprising one or more energy transfer donor and one or more energy transfer acceptor, linked through a molecular scaffold wherein the fluorescent molecules are separated along the scaffold to produce a unique fluorescence emission signature. The invention further provides for the use of said tags in multi-component analyses, including multiplex genetic analyses.

Abstract: The invention is directed primarily to compounds of Formula I: wherein: R1 is a polymeric residue; L1 is a bifunctional linking group; Y1 and Y2 are independently O, S or NR7; R2-7 are independently selected from the group consisting of hydrogen, C1-6 alkyls, C3-12 branched alkyls, C3-8 cycloalkyls, C1-6 substituted alkyls, C3-8 substituted cycloalkyls, aryls, substituted aryls, aralkyls, C1-6 heteroalkyls, substituted C1-6 heteroalkyls, C1-6 alkoxy, phenoxy and C1-6 heteroalkoxy; D is a moiety that is a leaving group or a residue of a compound to be delivered into a cell; Z is selected from the group consisting of: a moiety that is actively transported into a target cell, a hydrophobic moiety, and combinations thereof; Ar is a moiety which when included in Formula (I) forms a multi-substituted aromatic hydrocarbon or a multi-substituted heterocyclic group; and (y) is a positive integer greater than or equal to 1. Methods of making and using the same are also disclosed.

Abstract: A carrier for in vivo delivery of a therapeutic agent comprising a thiol group is provided, wherein the therapeutic agent is conjugated to the carrier via a biodegradable disulfide bond. Since extracellular fluids in vivo do not provide the appropriate environment to efficiently reduce a disulfide bond, while cellular cytosol does provide an appropriate environment, the agent will remain substantially coupled to the carrier while circulating through the body until the carrier crosses a cell membrane. As a result, the therapeutic agent is protected from degradation and renal clearance, and the potential for the therapeutic agent to elicit an immune response is limited.

Abstract: Cyclic homodetic peptides having a repeating D-L-chirality motif are shown to have a stable disk conformation with the amino acid side chains extending radially outward and the carbonyl and amino groups extending axially upward or downward. Such cyclic peptides can be employed as subunits in the assembly of molecular tubes. Cyclic peptides having a repeating D-L-chirality motif and lacking mutually repulsive side-chains are shown to stack atop one another in an anti-parallel fashion and are shown to be held together by the formation of &bgr;-sheet hydrogen bonding. The stacked cyclic peptides form a molecular tube having a central channel. The diameter of the channel is determined by the size cyclic peptide. If the cyclic peptide includes ionizable amino acid residues, e.g. glutamic acid or lysine, assembly and disassembly of the molecular tubes can be controlled by varying the pH. If the cyclic peptide includes hydrophobic amino acid residues, the molecular tube will insert into a lipid membrane.

Abstract: The present invention provides molecules that selectively home to various normal organs or tissues, including to lung, pancreas, skin, retina, prostate, ovary, lymph node, adrenal gland, liver or gut; and provides molecules that selectively home to tumor bearing organs or tissues, including to pancreas bearing a pancreatic tumor or to lung bearing a lung tumor. The invention also provides conjugates, comprising an organ or tissue homing molecule linked to a moiety. Such a moiety can be, for example, a therapeutic agent or a detectable agent. In addition, the invention provides methods of using an organ homing molecule of the invention to identify a particular organ or tissue by contacting the organ or tissue with a molecule of the invention.

Abstract: Compounds of the formula I R—Q—X  I, in which R, Q, and X are as defined herein, can be used as integrin inhibitors. In particular, compounds of formula I are suitable for the treatment of disorders caused by implants, defects, inflammations and of osteolytic disorders such as osteoporosis, thrombosis, cardiac infarct and arteriosclerosis. These compounds are also suitable for the acceleration and reinforcement of the integration process of implants and biocompatible surfaces into tissue.

Abstract: Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; 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 &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the: amino-terminus, 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: There is disclosed a process for purifying a natural product using a two-phase, multi-solvent system followed by vacuum concentration and back extraction. The method allows for the removal of impurities by controlling the polarity balance of a two-phase system by manipulating the proportions of the four solvents and subsequently the relative distribution of the product versus the impurities.

Abstract: The present invention encompasses radiolabeled peptide analogs of vasoactive intestinal peptide (VIP) labeled with a radionuclide useful for imaging target sites within mammalian living systems. The invention particularly provides radiolabeled VIP derivatives that bind selectively to the VIP receptor on target cells. Specifically, the invention relates to the radiolabeling of VIP-receptor specific agents and their subsequent use for radiodiagnostic and radiotherapeutic purposes. The invention encompasses methods for radiolabeling these peptides with radio-nuclides and the use of these peptides as scintigraphic imaging agents.

Abstract: An enzymatic synthesis and composition of &agr;-hydroxy carboxylic acid and &agr;-amino acid or peptide co-oligomers is disclosed wherein a residue of the &agr;-hydroxy carboxylic acid is linked to a residue of the &agr;-amino acid or peptide by an amide linkage. Proteolytic enzyme papain catalyzes co-oligomerization of the &agr;-hydroxy carboxylic acid and &agr;-amino acid. The degree and distribution of oligomerization varies upon the type and concentrations of different reaction mixtures utilized and upon the length of allowed reaction time. The resultant oligomers may be provided to ruminants as bioavailable amino acid supplements that are resistant to degradation in the rumen.

Abstract: Synthetic polypeptides from the conserved exposed region of streptococcal M protein are useful to prepare vaccines for oral or intranasal administration which will protect against streptococcal infection.

Abstract: The present invention provides a method for easily producing glycopeptides which are useful as a material for scientific studies, medicaments and foodstuffs. The glycopeptides can be produced by coupling a fluorinated glycoside of a monosaccharide or an oligosaccharide of the formula (I) with an amino acid or a peptide and then deprotecting the resultant glycopeptide by hydrogenation, and the sequential glycopeptide of the formula (IV) can be produced by polycondensation of a precursor glycopeptide.

Abstract: Disclosed herein are aggregating amyloid A&bgr; peptides which are covalently bonded (for example, at a cysteine amino acid residue) to a fluorescent label, and methods for their use.

Abstract: Novel activated peptides and conjugates thereof, useful in diagnostic assays and therapeutics, and processes for the preparation thereof are disclosed.

Abstract: Embodiments relate to the discovery that tripeptide amides, which correspond to viral capsid sequences, can be used to inhibit viral infection, including human immunodeficiency virus (HIV) infection. More specifically, medicaments comprising tripeptide amides and methods of using said compounds for the prevention and treatment of viral infection, such as HIV infection, are provided.

Abstract: A method is described for forming a crystalline Echinocandin nucleus salt from its mixed broth and/or partially purified process streams by the steps of nanofiltration to form a concentrate, addition of an aldehyde derivatizing agent which interacts with an aldehyde impurity, addition of an acid/metal salt to form a solubilized echinocandin nucleus salt having the desired anion, and subsequent cooling of the mixture to crystallize the salt.

Abstract: The present invention provides lipidized conjugates comprising an amino group-containing biologically active substance and a lipophilic group capable of penetrating a biological membrane. Under neutral or mildly acidic conditions, including those found in vivo, the free amino group-containing biologically active substance is released from the conjugate by hydrolysis of an amide bond. The present invention is also directed to methods of preparing lipidizing agents and lipidized conjugates, pharmaceutical compositions comprising lipidized conjugates and methods of increasing the delivery of amino group-containing substances into a cell. Preferred amino group-containing substances include peptides, proteins and derivatives thereof.

Abstract: The present invention relates to novel cyclosporins, processes for their preparation, their use as pharmaceuticals and pharmaceutical compositions comprising them. The novel cyclosporins are represented by the compound of formula I or a pharmaceutically acceptable salt thereof, wherein the letters A to L represent residues of amino acids.

Abstract: The present invention relates to a chemically modified polypeptide in which at least one of hydroxyl groups in the polypeptide molecule is modified with a polyalkylene glycol derivative; a method for producing the modified polypeptide; a method of treatment using the modified polypeptide; use of the modified polypeptide; a pharmaceutical preparation comprising the modified polypeptide; and a composition for treatment comprising the modified polypeptide.

Abstract: Compounds of the following formula are disclosed, wherein R1 is a peptide and R2 is an amino acid or peptide as disclosed herein: The compounds are inhibitors of activated protein C.

Abstract: Branched, substantially non-antigenic polymers are disclosed. Conjugates prepared with the polymers and biologically active molecules such as proteins and peptides demonstrate extended circulating life in vivo. Substantially fewer sites on the biologically active material are used as attachment sites. Methods of forming the polymer, conjugating the polymers with biologically active moieties and methods of using the conjugates are also disclosed.

Abstract: In accordance with the present invention, there are provided rapidly crosslinkable polypeptides which are obtained upon introduction of unsaturated group(s) into the polypeptide via linkage to amino acid residues on the polypeptide directly through one of three types of linkages, namely, an amide linkage, an ester linkage, or a thioester linkage. Each of these linkages are obtainable in a single step by use of a single derivatizing agent, acrylic anhydride. Also provided are methods for preparing such modified polypeptides and various uses therefor. It has unexpectedly been found that proteins with the above-described chemical modifications have the ability to rapidly crosslink to themselves under suitable conditions. This crosslinking occurs in the absence of any external crosslinking agents (indeed, in the absence of any extraneous agents), resulting in the formation of a solid gel material. Solid crosslinked gels are formed in seconds, starting from a freely flowing solution of polypeptide.

Abstract: Disclosed is an improved method for preparing an activated carboxylic acid in the form of a pentafluorophenyl ester, an improved method for making a carboxamide from a pentaflourophenyl ester, and a carboxamide and carboxamide library prepared using both of these methods.

Abstract: Methods are described for conjugating radioiodinated peptides or carbohydrate structures to proteins with improved yields and qualities of conjugates. In one method, specially designed radioiodinated bifunctional peptides containing nonmetabolizable amide bonds are coupled to antibodies. In a second method, radioiodinated nonmetabolizable bifunctional peptides, which also contain aminopolycarboxylates, are coupled to antibodies. In a third method, radioiodinated bifunctional aminopolycarboxylates are coupled to antibodies. In a fourth method, a hydrazide-appended antibody is coupled to a radioiodinated carbohydrate or a thiolated antibody is coupled to a hydrazide-appended and radioiodinated carbohydrate. In a fifth method a monoderivatized cyanuric chloride is used to conjugate thiolated antibody. Radioiodinated residualizing antibody conjugates made by these methods are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.

Abstract: Methods of preparing peptide linked oligomeric compounds are provided. The method is useful for preparing larger scale amounts of peptide linked oligomeric compounds. More particularly, the synthesis of peptide linked oligomeric compounds is performed without the problems of aggregation associated with electrostatic interactions. The present method describes using equimolar amounts of oligomeric compounds and peptide reagents providing for an increase in overall efficiency.

Abstract: The acetylation level of a peptide is determined utilizing the fact that the changes in the acetylation level are reflected in the sensitivity of the substrate peptide to a peptidase. This method can be used for measuring activities of deacetylase and acetylase, and also enables screening for substances that influence the activity of these enzymes. The deacetylase activity can be measured by a simple procedure according to the present invention.

Abstract: The present invention is directed to the improved synthesis of compounds of formula I: which may be useful in the treatment of prostate cancer. Such compounds are synthesized in the presence of a carboxyl activating agent, an additive and a base for the preparation of a PSA conjugate which comprises an anthracycline antibiotic and an oligopeptide.

Abstract: Provided are chains of precise length and methods for their preparation. These chains are formed by the reaction of a derivative of a diacid and a diamine in a stepwise manner on a support. One of the reactants contains a water soluble oligomer, preferably polyethylene glycol. These chains are then used to chemically modify target macromolecules such as biologically important polypeptides.

Abstract: The invention concerns immunogens, immunogenic compositions and method for the treatment of gastrin-dependent tumors. The immunogens comprise a peptide from the CCK-B/gastrin-receptor conjugated to a spacer and to an immunogenic carrier. The immunogens are capable of inducing antibodies in vivo which bind to the CCK-B/gastrin-receptor in tumor cells, thereby preventing growth stimulating peptide hormones from binding to the receptors, and inhibiting tumor cell growth. The immunogens also comprise antibodies against the CCK-B/gastrin-receptor for passive immunization. The invention also concerns diagnostic methods for detecting gastrin-dependent tumors in vivo or from a tissue biopsy using the antibodies of the invention.

Abstract: Compounds of the formula (1) or tautomers, stereoisomers or optical isomers thereof of the formula X—L—Y wherein X is paclitaxel or its derivative; L represents a linker having at least one functional group; and Y represents

Abstract: The present invention relates to insoluble compositions comprising a protein selected from the group consisting of insulin, insulin analogs, and proinsulins; a derivatized protein selected from the group consisting of derivatized insulin, derivatized insulin analog, and derivatized proinsulin; a complexing compound; a hexamer-stabilizing compound; and a divalent metal cation. Formulations of the insoluble composition are suitable for both parenteral and non-parenteral delivery for treating hyperglycemia and diabetes. Microcrystal forms of the insoluble precipitate are pharmaceutically analogous to the neutral protamine Hagedorn (NPH) insulin crystal form. Surprisingly, it has been discovered that suspension formulations of such insoluble compositions possess unique and controllable dissolution properties that provide therapeutically advantageous glucodynamics compared with insulin NPH formulations.

Abstract: Described are various human growth hormone releasing factor-PEG conjugates as well as their pharmaceutical use.

Abstract: A method of dewatering fine particulate materials is disclosed. In this method, an aqueous slurry of fine particles is treated with appropriate hydrophobizing reagents so that the particulate material becomes moderately hydrophobic. A lipid of vegetable or animal origin is then added to the slurry in solutions of light hydrocarbon oils and short-chain alcohols, so that the hydrophobic lipid molecules adsorb on the moderately hydrophobic surface and, thereby, greatly enhance its hydrophobicity. By virtue of the enhanced hydrophobicty, the water molecules adhering to the surface are destabilized and more readily removed during the process of mechanical dewatering. The moisture reduction can be further improved using appropriate electrolytes in conjunction with the lipids, spraying surface tension lowering reagents onto the filter cake, subjecting the cake to a suitable vibratory means, and using combinations thereof.

Abstract: A method of preparing lipoproteins, lipoaminoacids, lipid esters, and glucolipids from olive oil or one or more of its constituting fatty acids which are condensed with vegetal protein hydrolyzates or aminoacids or esterificated with alcohols or sugars, said fatty acids being chlorinated fatty acids of the olive oil.

Abstract: The present invention relates to a pharmaceutical composition for the nasal transmucosal delivery of a biocompatible polymer-biologically active peptide conjugate. The pharmaceutical composition of the present invention increases the water solubility of peptide, which is sparingly soluble in water, improves its stability by protecting it from being degraded by proteases. As a result, the number of administrations of the drug and the side-effects induced by drug abuse are decreased. In addition, since the pharmaceutical composition of the present invention is delivered through the nasal cavity, it allows drug activity to be expressed in a short period of time and improves a bioavailability.

Abstract: A method is described for separating and purifying a wide variety of fermentation cyclopeptide products containing at least one protonatable amino group (including the deacylated Echinocandin-type compounds) from their fermentation or mixed broths and partially purified process streams by adsorbing the mixture onto a hydrophobic, reversed phase chromatographic media and eluting with a continuous linear acetic acid gradient ranging from 0.1% acetic acid to 10.0% acetic acid by volume in water. A process for removing tripeptide-aldehyde by-products from the fermentation products by means of a derivatizing agent is also described.

Abstract: Polymers derived from polymers represented by Formula (A) (d is 20˜500; and Rs, which may be the same or different, represent each H, alkyl or benzyl) by substituting a part or all of the consisting peptide bonds by (1) hydrazino-Glu (Formula B), and saccharide-modified Glu (Formula C) or by (2) hydorazino-Glu (Formula B), and saccharide-modified Glu (Formula C), and drug bonded Glu (Formula D).

Abstract: Conjugates are prepared from antinociceptive agents, particularly opioids or opioid analogs, more particularly dynorphins, endorphins, deltorphins, enkephalins or analogs thereof, by combining said antinociceptive agent with a material providing a functionally reactive group capable of reacting with a blood component (preferably a blood cell or protein). Said conjugates permit extension of the therapeutic life of the antinociceptive agent. They may be administered to patients to alleviate pain, produce analgesic effects, or assist in cases of narcotics withdrawal, and may also be used as probes for receptor activity. The administration to the patient may be made either in vivo or ex vivo and may be performed by either introducing the derivative including the reactive functional group into the patient's vascular system or preparing such a conjugate externally (or in vitro) and introducing that conjugate to the patient's vascular system.

Abstract: The present invention is directed to novel peptidyl-2-amino-1-hydroxyalkanesulfonic acid inhibitors of cysteine proteases. Methods for the use of the protease inhibitors are also described.

Abstract: This invention provides efficient methods for producing a covalent linkage having improved chemical stability between an amine-containing biomolecule and a solid support or hydrogel surface containing an aldehyde moiety.

Abstract: The present invention is directed to a composition for causing photodynamic damage to target cells comprising a photosensitiser, a photosensitiser carrier component, a component which enables target cell recognition and transport of the photosensitiser toward the interior of the target cell by specific receptor-mediated endocytosis, and a component capable of effective targeted transport of the photosensitiser within the target cells. The invention is also related to a method for causing photodynamic damage to target cells comprising the steps of: adding the composition to the cells; keeping the cells at a temperature of normal vital activity of cells with the composition for causing photodynamic damage to the target cells, said composition comprising the above-mentioned components; and exposure of the cells to light.

Abstract: The invention relates to oligopeptide derivatives whose C-terminal amino acid is arginine which is linked to the remainder of an electroactive aniline or aminoquinoline derivative by an amide bond. The oligopeptide derivatives are split by enzymes of the class of peptide hydrolases, especially proteinases and their inhibitors, of the coagulation system, the fibrinolytic system and the complement system. These oligopeptide derivatives serve as substrates for quantitatively determining such enzymes, especially thrombin, in complex sample liquids, especially capillary blood. This determination is carried out by measuring the increase in the water-soluble amperogenic aniline or aminoquinoline compound. The oligopeptide derivatives and their salts can be produced according to usual methods in peptide chemistry.

Abstract: The invention realtes to improved liquid phase processes for the preparation of the 21 residue protein component, (Lys-Leu4)4-Lys, of the pulmonary surfactant KL-4. These process are amenable to large scale synthesis and one process employs a method of saponifying an ester which reduces the inherent racemization of the &agr;-carbon.

Abstract: This invention combines the unique antiplatelet effects of S-nitrosothiols and the antiadhesive properties of fragments of von Willebrand (vWF) in the A1 domain to provide unique molecules that exploit both of these properties. Preferred molecules comprise a fragment of A1 (Ala 444-Asn 730) in which arginine at position 545 is replaced by cysteine (the most frequent von Willebrand disease type 2b mutation) that has been discovered to impair platelet adhesion, and to inhibit an antithrombotic activity in vivo. This cysteine residue may be S-nitrosated to produce a novel molecule that has the potential for impairing platelet adhesion as well as activation/aggregation, and such molecules form the basis of a novel therapeutic method for impairing platelet responses following vascular injury or in other thrombotic disorders according to this invention.

Abstract: Processes for the preparation of modified proteins comprising the coupling of a first peptide segment having a haloacyl group at the N-terminus thereof with a second peptide sequent having a carbonylthiol group at the C-terminus thereof are disclosed. Novel modified proteins produced by the process are also disclosed.