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 compositions and methods for providing controllable local delivery of a conjugate of bortezomib (Btz) and a bisphosphonate to promote bone formation. In certain embodiments, the invention is used as a treatment for a subject with diseases and disorders characterized by bone loss.

Methods of treating aging related skin changes and of increasing skin thickness with topical administration of N-acyldipeptide derivatives and retinol are described. Combinations of retinol and N-acyldipeptide derivatives, are therapeutically effective for increasing skin thickness, and for treating extrinsic and intrinsic aging and aging related skin changes, such as fine lines, wrinkles, photoaging, hyperpigmentation, laxity, age spots, lentigines, mottled skin, and cellulite.

Some embodiments include compounds that can inhibit the growth of bacterial and/or inhibit or reduce microbial infections caused by one or more microorganisms (e.g., Pseudomonas aeruginosa and Cryptococcus neoformans) and methods of using these compounds to treat microbial infection and outbreaks and/or to reduce the formation of biofilms. Other embodiments include synthesis of the compounds that can inhibit the growth of one or more microorganisms and/or inhibit or reduce microbial infections.

The invention provides compounds of formula (I), that are peptidase enhanced cytotoxics. The invention further provides pharmaceutical compositions comprising the compounds, and the use of the compounds or pharmaceutical compositions as a medicament, particularly for use in the treatment or prophylaxis of cancers such as multiple myeloma, osteosarcoma, breast cancer, lung cancer, ovarian cancer, leukaemia and lymphoma.

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To provide a means capable of simultaneously and accurately analyzing a component derived from a carrier for liquid phase peptide synthesis with, for example, a target peptide.

A method for simultaneously analyzing a carrier for liquid phase peptide synthesis, a component derived from the carrier for liquid phase peptide synthesis, an amino acid to which the carrier for liquid phase peptide synthesis is bound, and a peptide compound to which the carrier for liquid phase peptide synthesis is bound, with a target peptide or final target peptide, the analysis method using high-performance liquid chromatography or supercritical fluid chromatography using an alcohol as an eluent.

The present invention relates to method for connecting a protein and a drug to a protein drug conjugate, wherein the drug is linked to the protein through a specific branched linker, said branched linker comprises a peptide chain and is derived from o-hydroxy p-amino benzylic alcohol, wherein the peptide chain is connected to the phenyl ring via the p-amino group, the drug is connected to the phenyl ring via the benzylic alcohol moiety, and the protein is connected to the phenyl ring via the o-hydroxy group; further to a process for the preparation of said protein-drug-conjugates via various intermediates, to the pharmaceutical use of such protein drug conjugates, such as methods of controlling the growth of undesirable cells, to pharmaceutical compositions comprising such protein drug conjugates, and to intermediates of the preparation of the protein drug conjugates.

The present invention provides an amphiphilic linear peptide and/or peptoid as well as a hy-drogel that includes the amphiphilic linear peptide/peptoid. The amphiphilic linear pep-tide/peptoid is capable of forming, a hydrogel. These peptides/peptoids include short amphi-philic sequences with a hydrophobic portion of aliphatic amino acids and at least one acidic, neutral, or basic polar amino acid. The amphiphilic linear peptide/peptoid is build up of non repetitive aliphatic amino acids, which may be in the L- or D-form. A plurality of such pep-tides/peptoids assembles to supramolecular helical fibers and forms peptide hydrogels after assembly: A corresponding hydrogel is formed in aqueous solutions at physiological pH and is thus useful for inter alia cell culture, tissue engineering, and drug release. Such hydrogels which are rigid, biocompatible and entrapping up to 99.9% of water are also well suited for applications utilizing electronic devices.

The present invention concerns a compound of following formula (I): where: R.sub.1 is H or OH, R.sub.2 is a (C.sub.1-C.sub.6)alkyl, COOH, COO((C.sub.1-C.sub.6)alkyl) or thiazolyl group, R.sub.3 is H or a (C.sub.1-C.sub.6)alkyl group, and R.sub.4 is: ?a straight-chain or branched, saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms substituted by one or more groups chosen from among OH and NR.sub.5R.sub.6, ?(CH.sub.2CH.sub.2X.sub.1)(CH.sub.2CH.sub.2X.sub.2).sub.a2(CH.sub.2CH.sub.2X.sub.3).sub.a3(CH.sub.2CH.sub.2X.sub.4).sub.a4(CH.sub.2CH.sub.2X.sub.5).sub.a5R.sub.7, ?an aryl-(C.sub.1-C.sub.8)alkyl group substituted by one or more groups chosen from among OH and NR.sub.9R.sub.10 groups, or ?a heterocycle-(C.sub.1-C.sub.8)alkyl group optionally substituted by one or more groups chosen from among (C.sub.1-C.sub.6)alkyl, OH and NR.sub.12R.sub.13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.

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A method of identifying an unknown spliced peptide derived from a known parent peptide contained in a biological sample, the method comprising: (1) a first step involving performing mass spectrometry on the sample to obtain mass spectrometry data regarding a peptide contained in the sample; (2) a second step involving searching a primary library, which is a database of known amino acid sequences, for an amino acid sequence that matches the mass spectrometry data, to identify a parent peptide contained in the sample, (3) a third step involving creating a secondary library including a candidate group of spliced peptides obtainable from the identified parent peptide; and (4) a fourth step involving searching the secondary library for an amino acid sequence that matches the mass spectrometry data, to identify a spliced peptide contained in the sample.