Abstract: A novel collagen mimic comprising a tripeptide unit having the formula (flpYaaGly)n, where flp is 4(S)-fluoro-L-proline, is disclosed. The collagen mimic has increased stability relative to the collagen-related triple helices (ProYaaGly)n, (hypYaaGly)n, and (HypYaaGly)n.

Abstract: A process for the solid phase synthesis of a peptide having at least one thyptophan residue, wherein said method comprises temporarily protecting the indole ring of said tryptophan residue with a side chain protecting group which is labile to a base wherein said protecting group is removed during cleavage of said peptide from the solid support.

Abstract: The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide having an isoleucine residue, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by an enzyme associated with the target cell. Methods of making and using the compounds are also disclosed.

Abstract: Hybrid proteins are described which comprise one or more antigen-binding antibody fragments covalently linked to one or more serum carrier proteins. The hybrid proteins can bind antigens, have a long half-life in vivo and can be used in medicine for therapy and diagnosis.

Abstract: The present invention relates generally to the field of analyzing proteins and more specifically to the reduction and alkylation of protein samples during protein analysis. A novel composition and method for reducing and alkylating proteins is disclosed. A novel reagent including a combination of a volatile reducing agent, a volatile alkylating agent, and a volatile solvent is used for a one-step reduction and alkylation of proteins allowing the protein sample to remain in the same container during the reduction and alkylation processes.

Abstract: The invention relates to a method of preventing gel formation of a hydrophobic peptides by contacting the hydrophobic peptide with a counter-ion in an amount and at a molar ratio with the peptide that are sufficient to provide a fluid, milky microcrystalline aqueous suspension of the peptide without formation of a gel. The invention also relates to a fluid, milky microcrystalline aqueous suspension of a hydrophobic peptide and a counter-ion in water, wherein the peptide and counter-ion are present in amounts and at a molar ratio sufficient to form, upon mixing, the suspension without formation of a gel.

Abstract: The present invention relates to the preparation of polyethylene glycol carbonate active esters useful for the PEGylation of biological active and pharmaceutically useful peptides and proteins. The invention involves the use of activated carbonate and oxalate esters in the formation of polyethylene glycol mixed carbonate active esters that then react with a linker or directly with a target peptide or protein.

Abstract: The invention provides biologically active erythropoietin (EPO) conjugate compositions wherein EPO is covalently conjugated to a non-antigenic hydrophilic polymer covalently linked to an organic molecule that increases the circulating serum half-life of the composition. The invention thus relates to EPO derivatives described by the formula EPO-(X-Y)N where EPO is erythropoietin or its pharmaceutical acceptable derivatives having biological properties of causing bone marrow cells to increase production of reticulocytes and red blood cells, X is PEG or other water soluble polymers, Y is an organic molecule that increases the circulating half-life of the construct more than the PEG alone and N is an integer from 1 to 15. Other molecules may be included between EPO and X and between X and Y to provide the proper functionality for coupling or valency.

Abstract: The present invention relates to cell adhesion promoting (“CAP”) peptide combinations that promote cell attachment or cell adhesion to culture surfaces that are otherwise cell adhesion resistant “CAR”. The invention provides combination of peptides that, when covalently coupled to a CAR layer such as hyaluronic acid that has been created on a polystyrene surface, promote cell attachment, growth differentiation, and execution of other desired cellular functions in culture.

Abstract: Synthesis routes that can be adapted to large scale synthesis of oligoguanidine compounds such as oligoarginine compounds are described which use a perguanidinylation step to convert a group of ?-amino groups to the corresponding guanidinyl groups. These compounds find utility as transport agents. Modified oligoguanidine compounds are also described.

Abstract: The present invention discloses peptide substrates of a proteolytic ADAM33 polypeptide. The present invention also discloses methods of identifying additional substrates of a proteolytic ADAM33 polypeptide. Furthermore, the present invention discloses methods of identifying compounds that inhibit the proteolytic activity of a proteolytic ADAM33 polypeptide.

Abstract: The present invention relates to a GLP-1 peptide having the following formula, or a pharmaceutically acceptable salt thereof: X-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-lle-Ala-Trp-Leu-val-Lys-Gly-Arg-Y (SEQ ID NO. 1) wherein X is a rigidifying hydrophobic moiety and wherein Y is selected from the group consisting of OH, NH2 and Gly-OH. Moreover, the present invention relates to pharmaceutical compositions comprising a therapeutically effective amount of a peptide of the present invention, or a pharmaceutically acceptable salt thereof, in association with at least one constituent selected from a pharmaceutically acceptable carrier, diluent, and excipient.

Abstract: The present invention relates to active agent delivery systems and more specifically to compositions that comprise amino acids, as single amino acids or peptides, covalently attached to active agents and methods for administering conjugated active agent compositions.

Abstract: Interleukin-10 (IL-10) conjugated via a linker to one or more polyethylene glycol (PEG) molecules at a single amino acid residue of the IL-10, and a method for preparing the same, are provided. The method produces a stable mono-pegylated IL-10, which retains IL-10 activity, where pegylation is selective for the N-terminus on one subunit of IL-10 with little or no formation of monomeric IL-10. The method also provides a substantially homogenous population of mono-PEG-IL-10.

Abstract: Synthetic peptides and derivatives thereof capable of inhibiting the biological activity of anti-beta-2-glycoprotein 1 (?2GPI) monoclonal antibodies (mAbs) in vitro, and of inhibiting induction of experimental anti-phospholipid syndrome (APS) in mice by anti-?2GPI mAbs, are provided for the diagnosis and treatment of anti-phospholipid syndrome in humans.

Abstract: Metallopeptides and metallopeptide combinatorial libraries specific for melanocortin receptors are provided, for use in biological, pharmaceutical and related applications. The metallopeptides and combinatorial libraries are made of peptides, peptidomimetics and peptide-like constructs, in which the peptide, peptidomimetic or construct is conformationally fixed on complexation of a metal ion-binding portion thereof with a metal ion.

Abstract: The present invention provides specific peptides identified as having cell adhesion, growth, expression or secretion-enhancing activities. Many of the peptides of the invention may be produced in large quantity by such means as chemical synthesis or recombinant DNA methodology. They may be non-specifically adsorbed, or chemically attached to a surface or, alternatively, formulated in a culture medium to produce the desired effect on cultured cells.

Abstract: The compound (W-Z-M) according to the invention comprises a component (M) chosen from the group consisting of markers and therapeutic agents possessing an intracellular active site (A.S.), linked to a ligand (W-Z) comprising an arm (Z) linked to a terminal group (W), characterized in that the linkage between the arm (Z) of the ligand (W-Z) and the component (M) prevents intracellular entry of the compound (W-Z-M) and/or inhibits expression of the marker (M), in that said linkage can be selectively cleaved by factors secreted by target cells so as to permit expression of the marker (M) or entry of the therapeutic agent (M) into said target cells, and in that the terminal group (W) provides for the stability of the compound (W-Z-M) in the serum and circulating blood.

Abstract: The present invention concerns methods and compositions for extending the technique of native chemical ligation of a wider range of peptides, polypeptides, other polymers and other molecules via an amide bond (see FIG. 1). The invention further provides methods and uses for such proteins and derivatized proteins. The invention is particularly suitable for use in the synthesis of optionally polymer-modified, synthetic bioactive proteins, and of pharmaceutical compositions that contain such proteins.

Abstract: The present invention relates generally to hydrolyzable drug-oligomer conjugates, pharmaceutical compositions comprising such conjugates, and to methods for making and using such conjugates and pharmaceutical compositions. For example, a conjugate of insulin, PEG, and oleic acid can be orally administered.

Abstract: Molecules having potential biological activity, particularly peptoids, that are conjugated to solid phase supports, spacer groups, and/or ligation moieties, and methods of their preparation, are described. In some instances, the molecules of the invention are made entirely by solid phase synthesis. In other instances, the spacer groups are hydrophilic and compositions containing them, and to solid phase synthesis of varied structure peptoids using chemoselective ligation moieties.

Abstract: Site-specific modified proteins and method for producing site-specific modified proteins using amino acid analogs are disclosed. Methods for labeling proteins at a desired site in the presence of nucleophilic side chains, including lysine and cysteine side chains, are also disclosed. Methods for labeling the site-specific modified proteins are also disclosed.

Abstract: The present invention relates to a method of applying mass spectrometry to analyzing peptides or proteins, especially in the proteome setting. More particularly, the invention relates to a mass spectrometry-based method for detection of protein/peptide phosphorylation wherein the side chains of glutamic acid and/or aspartic acid residues of said peptides or proteins are chemically modified as to improve the selectivity/efficiency of identification of the phosphorylated protein/peptide.

Abstract: This invention relates to retroviral regulatory proteins or fragments thereof, or interferon alpha protein or fragments thereof, which are carboxymethylated. This chemical modification leads to new proteins or fragments which are biologically inactive but preserve their immunogenicity (toxoids). These proteins or fragments thereof, or interferon alpha or fragments thereof, can be utilized in the treatment and prevention of retroviral infections. The invention also relates to a pharmaceutical composition comprising at least one carboxymethylated protein or fragment of the invention, together with a pharmaceutically acceptable carrier. The invention also relates to a vaccine comprising at least one of the carboxymethylated proteins or fragments of the invention, together with an immunologically acceptable carrier. The invention also relates to a process for obtaining an immunogenic yet not toxic retroviral regulatory protein or fragment, or interferon alpha or fragment.

Abstract: A method is provided for preparing a biologically active molecule having an increased serum half-life. The method involves conjugating a polymer such as polyethylene glycol to the biologically active molecule. Also provided are polypeptide drugs having an increased serum half-life, e.g., human urokinase plasminogen activator (human “uPA” or “hUPA”) or a fragment or derivative thereof. Pharmaceutical compositions containing such molecules and methods of using them to treat uPA-mediated and uPA receptor-mediated disorders are also provided.

Abstract: An process for the reversible modification of membrane interaction of a compound is described. Modification of membrane interaction can be used to facilitate delivery of molecules to cells in vitro and in vivo. The described modifiers, which are used to reversibly inactivate the membrane active compounds, can also be utilized as cross-linkers or to reverse the charge of a molecule.

Abstract: A pro-drug comprising a cyclic undecapeptide wherein the peptide chain thereof comprises at least one amino acid residue, useful as a medicinal product, including use for treatment of pathological conditions of the eye.

Abstract: Disclosed herein is a process for promoting the integration of a biocompatible device or implant into a tissue of a subject. The process comprises covalently bonding to the surface of the device or implant a compound of the formula I R-Q-X??I wherein R is cyclo-(Arg-Gly-Asp-Z), and wherein Q, X and Z are as defined herein.

Abstract: The present invention relates to a novel drug delivery system of use in the improved delivery of drug therapeutic agents into target cells. The system comprises a drug moiety linked to a carrier moiety wherein the carrier moiety comprises a homeobox peptide or a fragment or derivative thereof.

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: The invention is directed to nucleophile-stable thioester generating compounds comprising a carboxyester thiol. The compounds have wide applicability in organic synthesis, including the generation of peptide-, polypeptide- and other polymer-thioesters. The invention is particularly useful for generating activated-thioesters from precursors that are made under conditions in which strong nucleophiles are employed, such as peptides or polypeptides made using Fmoc SPPS, as well as multi-step ligation or conjugation schemes that require (or benefit from the use of) compatible selective approaches for directing a specific ligation or conjugation reaction of interest.

Abstract: Pharmaceutical, personal care and cosmetic compositions containing a tripeptide and a tetrapeptide are useful for treating visible signs of aging including wrinkles, stretch marks and dark circles.

Abstract: The present invention relates to a method of simultaneously identifying and determining the levels of expression of cysteine-containing proteins in normal and perturbed cells, a method for proteomic analysis, a process for preparing fusion proteins, and compounds of Formula II and III: (II) Acyl-NH—X-[Epitope Tag Site]A-Y-[Protease Cleavage Site]-Z-Link (III) Acyl-NH—X-alk-O-Ph-CH2—Z-Link and reagents related thereto.

Abstract: Proteins are derivitized by reaction of pendant groups, usually groups which are side chains in non-terminal amino acyl units of the protein, in aqueous reactions in the presence of a denaturant. The denaturant is preferably an amphiphilic compound, most preferably an anionic amphiphilic compound such as a long chain alkyl sulphate mono ester, preferably an alkaline metal salt, for instance sodium dodecyl sulphate. The degree of derivatization is increased, while the protein retains activity, such as enzyme activity. The increase in the degree of derivatization enhances the increase in circulation time in vivo and stability on storage and in vivo. Preferably the derivatizing reagent is an aldehyde compound which reacts with primary amine groups, generally the epsilon-amino group of lysyl units. Derivatization is conducted under reducing conditions to generate a secondary amine derivative.

Abstract: This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are highly stable and readily administered via an oral route.

Abstract: A process for treating organic compounds includes providing a composition which includes a substantially mesoporous structure of silica containing at least 97% by volume of pores having a pore size ranging from about 15 ? to about 30 ? and having a micropore volume of at least about 0.01 cc/g, wherein the mesoporous structure has incorporated therewith at least about 0.02% by weight of at least one catalytically and/or chemically active heteroatom selected from the group consisting of Al, Ti, V, Cr, Zn, Fe, Sn, Mo, Ga, Ni, Co, In, Zr, Mn, Cu, Mg, Pd, Pt and W, and the catalyst has an X-ray diffraction pattern with one peak at 0.3° to about 3.5° at 2?. The catalyst is contacted with an organic feed under reaction conditions wherein the treating process is selected from alkylation, acylation, oligomerization, selective oxidation, hydrotreating, isomerization, demetalation, catalytic dewaxing, hydroxylation, hydrogenation, ammoximation, isomerization, dehydrogenation, cracking and adsorption.

Abstract: This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis and/or other pathologies characterized by an inflammatory response. In certain embodiment, the peptides resemble a G* amphipathic helix of apolipoprotein J. The peptides are highly stable and readily administered via an oral route.

Abstract: The present invention relates to certain biologically active peptides and polypeptides which can be used as therapeutics or prophylactics against diseases or disorders linked to NGF as the causative agent. In one aspect of the present invention, pharmacologically active polypeptides comprising peptides linked to one or more Fc domains are provided.

Abstract: Disclosed are ?-peptides and ?-peptide conjugates that are capable of diffusing or otherwise being transported across the cell membranes of living cells. The ?-peptides contain at least six ?-amino acid residues, at leastsix of which are preferably ?3-homoarginine residues. It has been found that when pharmacologically-active agents are conjugated to these types of ?-peptides, the resulting conjugates (also disclosed herein) are also capable of diffusing or otherwise being transported across the cell membranes of living cells, including mammalian cells.

Abstract: The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the CD10 enzyme. Methods of treatment using the prodrug and methods of designing a prodrug are also disclosed.

Abstract: The present invention provides a modified lactoferrin peptide which is cytotoxic, 7 to 25 amino acids in length, with three or more cationic residues and which has one or more extra bulky and lipophilic amino acids as compared to the native lactoferrin sequence, as well as esters, amides, salts and cyclic derivatives thereof as well as methods of preparing such peptides, pharmaceutical compositions containing such peptides and use of the peptides as medicaments, particularly as antibacterials or anti-tumoural agents.

Abstract: This invention relates to new polypeptide compound represented by the general formula (I) wherein R1, R2, R3, R4, R5 and R6 are as defined in the description or a salt thereof which has antimicrobial activities (especially, antifungal activities), inhibitory activity on ?-1,3-glucan synthase, to process for preparation thereof, to a pharmaceutical composition comprising the same, and to a method for prophylactic and/or therapeutic treatment of infectious diseases including Pneumocystic carinii infection (e.g. Pneumocystis carinii pneumonia) in a human being or an animal.

Abstract: The present invention relates to novel amphipathic peptide-conjugated oligomeric compounds and to methods of making and using such compounds. The invention further relates to methods of enhancing the cellular uptake of oligomeric compounds comprising conjugating the compounds to amphipathic moieties such as amphipathic peptides.

Abstract: Amphiphilic lipopeptide compositions for gene delivery are disclosed. An illustrative amphiphilic lipopeptide composition includes a human protamine 2 peptide conjugated to a hydrophobic moiety. Illustrative hydrophobic moieties include sterols, bile acids, and fatty acids. The amphiphilic lipopeptide composition is mixed with a nucleic acid such that the nucleic acid binds to the peptide portion of the lipopeptide. This mixture is placed in contact with mammalian cells to effect transfection of the cells with the nucleic acid. A method of making such amphiphilic lipopeptides is also described.

Abstract: A method is described for the site-specific preparation of hGRF-PEG conjugates containing one or more PEG units (per mole of hGRF) covalently bound to Lys12 and/or Lys21 and/or N?, characterized in that the conjugation reaction between the hGRF peptide and activated PEG is carried out in solution and the desired hGRF-PEG conjugate can be purified by chromatography. The conjugates prepared by this method, as well as their use in the treatment, prevention or diagnosis of growth hormone deficiency, are also an object of the present invention.

Abstract: The present invention relates to a process for the preparation of peptides using an excess of an activated carboxylic component to acylate an amino component, wherein after the acylation an amine comprising a free anion or a latent anion is used as a scavenger of residual activated carboxylic functions. This process is useful for the preparation of oligo- and polypeptides and, more generally, in the preparation of compounds containing one or more amide bonds.

Abstract: Methods are described for conjugating radioiodinated non-metabolizable peptides to proteins and antibodies with improved yields and qualities of conjugates. Radioiodinated residualizing antibody conjugates comprising any aminopolycarboxylate-appended peptide, or any carbohydrate-appended peptide, are also provided. Additionally, methods are described for conjugating radioiodinated aminopolycarboxylates to proteins and antibodies, as well as for conjugating radioiodinated non-metabolizable carbohydrates to proteins and antibodies by a variety of chemical approaches. The instant radioiodinated residualizing antibody conjugates are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.

Abstract: A non-polydispersed mixture of conjugates in which each conjugate in the mixture comprises a drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may result in less inter-subject variability than polydispersed mixtures of similar conjugates.

Abstract: A nanowire comprising only metal having an average length of 1 ?m or more which could not be produced in the prior art, and a method of manufacturing this wire. This invention provides a method of manufacturing a metal nanowire, which comprises the step of reducing a nanofiber comprising a metal complex peptide lipid formed from the two-headed peptide lipid represented by the general formula (I): in which Val is a valine residue, m is 1-3 and n is 6-18, and a metal ion, using 5-10 equivalents of a reducing agent relative to the two-headed peptide lipid. It further provides a metal nanowire having an average diameter of 10-20 nm and average length of 1 ?m or more. It is preferred that the metal is copper.

Abstract: The present invention relates to an antagonist of the ligand of the Corticotropin-Releasing Factor Receptor, type 2 (CRFR2) lacking the 8 to 10 N-terminal amino acids of native sauvagine. The present invention also relates to an antagonist of the ligand of the Corticotropin-Releasing Factor Receptor, type 2 (CRFR2) lacking the 11 N-terminal amino acids of native sauvagine, wherein the N-terminal amino acid of said antagonist is a charged amino acid. Furthermore, the present invention relates to a polynucleotide encoding the antagonist of the present invention, a vector comprising the polynucleotide of the present invention, and a host comprising the polynucleotide or the vector of the present invention. Also described are a method for producing the antagonist of the present invention, antibodies directed the antagonist of the present invention, as well as anti-idiotypic antibodies directed against the antibody of the present invention.