This invention relates to a novel method for producing di-chain proteins for use in humans from single-chain precursors, including di-chain clostridial neurotoxins. The method comprises the step of expressing a nucleic acid sequence encoding a single-chain precursor comprising a thrombin-cleavage site and the step of cleaving the single-chain precursor with a human factor Xa or a human thrombin, particularly a human thrombin drug product authorized for human therapeutic use. The invention further relates to novel di-chain clostridial neurotoxins and nucleic acid sequences encoding such novel di-chain clostridial neurotoxins.

The present application provides novel compounds of the Formula (I), pharmaceutical compositions comprising such compounds and methods for using such compounds as tools for biological studies or as agents or drugs for modulating Protease Activated Receptor-2 (PAR2) and for treating a subject at risk ofor susceptible toa disease or disorder, or having a disease or disorder associated with undesirable PAR2 activity.

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Process for the separation of a biomolecule containing at least one cationic group from a liquid medium containing said biomolecule, which comprises the use of a tetraphenylborate (TPB) salt.

Inhibitors of fibroblast activation protein alpha (FAP) and Prolyl Oligopeptidase (POP) are disclosed, along with their use in various therapies related to conditions, diseases, and disorders involving abnormal cell proliferation such as malignancies and angiogenesis, and in neural disorders such as Alzheimer's disease. Stalk portions of the inhibitor molecules, and substrates of FAP and POP, are also disclosed and may be used, for example, in screening methods for identifying such inhibitors.

The present invention provides compounds and pharmaceutical compositions of a peptidomimetic ligand, e.g. LLP2A, conjugated with a bisphosphonate drug, e.g. Alendronate. The compounds and pharmaceutical compositions of the present invention are useful in the treatment of osteoporosis and for the promotion of bone growth due to their specificity for the .sub.4.sub.1 integrin on mesenchymal stem cells and for the surface of bone.

Ligands that bind to prion proteins and methods for using the ligands for detecting or removing a prion protein from a sample, such as a biological fluid or an environmental sample. The ligands are capable of binding to one or more forms of prion protein including cellular prion protein (PrPc), infectious prion protein (PrPsc), and recombinant prion protein (PrPr). Prions from various species, including humans and hamsters, are bound by the ligands. Also provided is a method of treating or retarding the development of a prion-associated pathology in a subject.

The peptides have the general following formula: X-Pro*-Pro*-Xaa-Y in which: Xaa is selected from Leucine (Leu, L), Arginine (Arg, R), Lysine (Lys, K), Alanine (Ala, A), Serine (Ser, S), and Aspartic acid (Asp, D); At the N terminal end of the peptide, X is selected from H, COR1 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 and NR.sub.1R.sub.2; R.sub.1 and R.sub.2 are, 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 sulfured, and which skeletum can comprise an heteroatom, in particular an O, S and/or N atom; Pro* correspond to a Proline, an analogue or derivative thereof; if X is H then Y is selected from OR.sub.1, NH.sub.2, NHR.sub.1 and NR.sub.1R.sub.2, and if Y is OH then X is CO or SO.sub.2R.sub.1; and the peptide hypoxanthine-Pro-Pro-Arg being excluded. The invention provides the use of the peptides of above formula I to stimulate the synthesis of the molecules constituting the dermal extracellular matrix, including collagen I and IV and elastin. A cosmetic treatment according to the invention includes anti-aging, anti-wrinkles, improving mechanical properties of the skin, firmness/tone/elasticity/suppleness/flexibility, increasing density and volume of the skin, restructuring effect, fighting stretch marks, improving skin barrier and/or skin hydration.

The present invention relates to a new class of compounds based on alkylated oligopeptides featuring distinct head and tail modifications at their termini. The compounds are useful as inhibitors of viral proteases, particularly of flaviviral proteases, and can therefore be used for treatment of viral infections.

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.