The present invention relates to a GABA.sub.A receptor-binding peptide comprising an amino acid sequence X.sub.1-X.sub.2-X.sub.3-X.sub.4-X.sub.5, wherein the amino acid residue X.sub.1 is histidine, arginine, threonine, L-cyclohexyl-alanine, 2-flouro-L-phenylalanine or 3-methyl-L-histidine; X.sub.2 is threonine, N-methyl-threonine, proline, leucine, isoleucine or phenylalanine; X.sub.3 is tryptophan, N-methyl-tryptophan, serine, threonine or proline; X.sub.4 is glutamine, proline, lysine, tyrosine, alanine, glycine or absent; and X.sub.5 is lysine, glutamic acid, aspartic acid, threonine, alanine, glycine or absent. In particular, the GABA.sub.A receptor-binding peptides of the present invention have amino acid sequences selected from SEQ ID NOs: 1 to 15. These peptides were tested and validated using electrophysiological recordings on the human GABA.sub.A receptor comprising of the following subunits .sub.1.sub.3.sub.2 and used in the preparation of a neuroactive pharmaceutical composition, in improving sperm motility or in labeling of biomolecules.

The present invention relates to use of peptides as a therapeutic agent, wherein it has been confirmed that the peptides of the present invention significantly inhibit the activity of T cells and the differentiation of T helper 17 cells (Th17 cells), which are associated with autoimmune disease, reduce the secretion of inflammatory cytokine IL-6, and have remarkable effects of treating and improving arthritis in an animal model of arthritis. Therefore, the peptides may be used as an active ingredient in therapeutic agents for various autoimmune diseases such as bone disease, inflammatory disease or rheumatoid arthritis.

The invention is directed to the use of at least one peptide of formula: X-(Xaa.sub.1).sub.n-Pro*-(Xaa.sub.2).sub.m-Y (I) With: -n=0, 1 or 2; -m=0 or 1 and if m=0 then n0 -Xaa.sub.1 is: -An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; -A polar aminoacid selected from Serine (Ser, S), Threonine (Thr, T), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q) and analogues and derivatives thereof; -or Glycine (Gly, G); When n=2 the two aminoacids Xaa.sub.1 can be the same or different; -Xaa.sub.2 is: -An hydrophobic aminoacid selected from Alanine (Ala, A), Valine (Val, V), Methionine (Met, M), Leucine (Leu, L), Isoleucine (Ile, I), Phenylalanine (Phe, F), Proline (Pro, P) and analogues and derivatives thereof; -A basic aminoacid selected from Arginine (Arg, R), Lysine (Lys, K) and Histidine (His, H) and analogues and derivatives thereof; -Glycine (Gly, G) or Serine (Ser, S); -At the N terminal end of the peptide, X is selected from H, COR.sub.1 and SO.sub.2R.sub.1; -At the C terminal end of the peptide, Y is selected from OH, OR.sub.1, NH.sub.2, NHR.sub.1 or NR.sub.1R.sub.2, R.sub.1 and R.sub.2 being independently from each other, selected from an alkyle, aryle, aralkyle, alkylaryl, alkoxy and aryloxy group, that can be linear, branched, cyclic, poly-cyclic, non-saturated, hydroxylated, carbonylated, phosphorylated and/or sulphured, with the possibility to have in said group skeleton a O, S and/or N heteroatom; -Pro* corresponding to a Proline, an analogue or derivative thereof; Excluding the peptides where X=H and Y=OH, for a non therapeutical cosmetic pro-pigmenting treatment of skin. The invention also encompasses new tripeptides of formula (I) suitable for a non therapeutical cosmetic treatment of skin.

A water-soluble peptide fluorescence material having a structure of formula (I): ##STR00001## In formula (I), n is an integer greater than or equal to 1, R.sub.1 is independently selected from hydrogen or a nitrogen-containing functional group, R.sub.2 is independently selected from hydrogen or alkyl, and A.sub.1 is polymerized by at least one amino acid monomer and having a structure of formula (II): ##STR00002## In formula (II), m is an integer greater than or equal to 1, and R.sub.3 in each of the amino acid monomers of A.sub.1 is independently selected from hydrogen, alkyl, aralkyl, alkylthioaalkyl, hydroxyaralky, heteroaralkyl, carboxylalkyl, or guanidinylalkyl. A.sub.2 is OR.sub.5 or N(R.sub.4).sub.2, and R.sub.4 is independently selected from hydrogen, alkyl, aralkyl, alkylthioaalkyl, hydroxyaralky, heteroaralkyl, carboxylalkyl, guanidinylalkyl, monoglycosyl, biglycosyl, or oligosaccharyl, and R.sub.5 is hydrogen, alkyl, aralkyl, alkylthioaalkyl, hydroxyaralky, heteroaralkyl, carboxylalkyl, or guanidinylalkyl.

Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.

Provided herein are tripeptide epoxy ketone protease inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (X):

##STR00001##

and pharmaceutically acceptable salts and compositions including the same. The compounds and compositions provided herein may be used, for example, in the treatment of diseases including inflammation and neurodegenerative disease.

Processes for preparing compounds of Formula (1) and Formula (2) are described, wherein X, Y, Z, R.sub.1-R.sub.7, L and n are defined herein. Intermediates useful in the preparation of the compounds of Formula (1) and Formula (2) are also described. ##STR00001##

This disclosure features compounds that are useful as pro-drugs of epoxy ketone protease inhibitors.

The present invention provides a process for the liquid phase synthesis of the Ghrelin analog H-Inp-(D)Bal-(D)Trp-Phe-Apc-NH.sub.2 (SEQ ID NO: 1, Formula (I)), pharmaceutically acceptable salts thereof.

The present invention provides bivalent and multivalent ligands with a view to improving the affinity and pharmacokinetic properties of a urea class of PSMA inhibitors. The compounds and their synthesis can be generalized to multivalent compounds of other target antigens. Because they present multiple copies of the pharmacophore, multivalent ligands can bind to receptors with high avidity and affinity, thereby serving as powerful inhibitors. The modular multivalent scaffolds of the present invention, in one or more embodiments, contains a lysine-based (-, -) dialkyne residue for incorporating two or more antigen binding moieties, such as PSMA binding Lys-Glu urea moieties, exploiting click chemistry and one or more additional lysine residues for subsequent modification with an imaging and/or therapeutic nuclides or a cytotoxic ligands for tumor cell killing.