Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.

Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of a therapeutic biological molecule, and/or naturally or artificially occurring derivatives, analogues, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide). The present technology provides compositions related to aromatic-cationic peptides linked to a therapeutic biological molecule and uses of the same. In some embodiments, the aromatic-cationic peptide comprises 2,6-dimethyl-Tyr-D-Arg-Phe-Lys-NH.sub.2, Phe-D-Arg-Phe-Lys-NH.sub.2, or D-Arg-2,6-Dmt-Lys-Phe-NH.sub.2.

Disclosed are proteasome inhibitors, fibroblast activation protein (FAP)-activated prodrugs of proteasome inhibitors, and pharmaceutically acceptable salts of the inhibitors and prodrugs. Also disclosed are related pharmaceutical compositions, and methods of using the inhibitors and prodrugs and compositions thereof, for example, in treating cancer or other cell proliferative diseases. In vitro and in vivo methods of quantifying the expression of FAP in a biopsy sample and a mammal, respectively, are also disclosed.

The present invention relates to peptidomimetics of the formula (I) or (I)c wherein L.sub.1, L.sub.2, L.sub.3, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, n, m, Q, X, Z.sub.1 and Z.sub.2 are defined as mentioned in the description and to salts and solvates of each of these compounds and to processes for the preparation thereof, compositions containing them and the uses of such compounds. It has been found that the compounds have a high microbicide activity and are suited to combat resistant bacteria, such as meticillin-resistant Staphylococcus aureus (MRSA) strains, at very low concentrations.

The present disclosure provides assays for lysosomal enzymes, specifically palmitoyl protein thioesterase 1 (PPT1) and tripeptidyl peptidase 1 (TPP1), using, for example, tandem mass spectrometry. The assays involve the detection of enzymatic products obtained through the action of the lysosomal enzymes on new enzyme substrates, and can be used for quantitative enzyme activity measurements. The assays for the enzymes utilize a minimum steps for sample work up and can be run in a simplex format or in a duplex format for the detection of neuronal ceroid lipofuscinoses, or in a multiplex format with other mass spectrometry-based assays for screening of neuronal ceroid lipofuscinoses and other lysosomal storage disorders.

The invention relates to a peptide comprising (i) a main chain comprising at least one L-3,4-dihydroxyphenylalanine (DOPA), (ii) at least one integrin binding peptide, and (iii) at least one heparin binding peptide. The invention further relates to a coating for metal surfaces comprising the peptide according to the invention and a coated metal surface which promotes osseointegration that can be obtained by reacting the peptide according to the invention with a metal surface.

The present invention relates to 1,2,4-oxadiazole compounds of formula (I) and their use to inhibit the programmed cell death 1 (PD-1) signaling pathway and/or for treatment of disorders by inhibiting an immunosuppressive signal induced by PD-1, PD-L1 or PD-L2.

Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

A method for producing a peptide by conducting steps (1) condensing an N-protected amino acid or an N-protected peptide to an N-terminus of a C-protected amino acid or a C-protected peptide represented by formula (II):

##STR00001##

wherein Y represents an amino acid or a peptide with an unprotected N-terminus; R.sup.1, R.sup.2 and R.sup.3 each independently represent an optionally substituted aliphatic hydrocarbon group, an optionally substituted aromatic hydrocarbon group, or OR.sup.4 (wherein R.sup.4 represents an optionally substituted aliphatic or aromatic hydrocarbon group; two of R.sup.1, R.sup.2 and R.sup.3 may form a 5- to 7-membered ring together with the Si atom to which they are bonded; and the R.sup.1R.sup.2R.sup.3Si group has 8 or more carbon atoms and is bonded to a C-terminus of an amino acid or a peptide in Y, and (2) removing the protective group at the N-terminus of the peptide obtained in step (1).

Described are: [1] a compound or the like represented by the formula (1); [2] a compound or the like having a target molecule recognition element bound to the compound or the like described in the above [1]; and [3] a metal complex compound or the like having a metal selected from the group consisting of a radioactive metal and a radioactive atom-labeled metal, and the compound or the like described in the above [1] or [2] coordinated to the metal. Also described are uses of the compound or the like described in the above [1] or [2] or the metal complex compound or the like described in the above [3] in a radioactive drug, a radiotherapeutic agent or a radioactive diagnostic imaging agent.

##STR00001##