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.

The invention relates to synthetic peptide amide ligands of the kappa opioid receptor and particularly to agonists of the kappa opioid receptor that exhibit low P.sub.450 CYP inhibition and low penetration into the brain. The synthetic peptide amides of the invention conform to the structure:

##STR00001##

The compounds are useful in the prophylaxis and treatment of pain and inflammation associated with a variety of diseases and conditions.

Compounds of formula (I) as inhibitors of DCN1 and compositions containing the same are disclosed. Methods of using the DCN1 inhibitors in the treatment of diseases and conditions wherein inhibition of DCN1 provides a benefit, like oxidative stress-related diseases and conditions, neurodegenerative diseases and conditions, metabolic disorders, and muscular nerve degeneration, also are disclosed. ##STR00001##

The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.

The disclosure pertains to methods of treating or preventing a disease or condition associated with and/or induced by soluble A-beta oligomer such as Alzheimer's disease by administering to a subject in need thereof conformation specific and/or selective antibodies or binding fragments thereof and related products.

Provided is a peptide having an ability to inhibit binding between amylospheroids (ASPD) and neurons. In one aspect, provided is a synthesized, isolated, or purified polypeptide represented by Formula (I) or (II) below: X.sub.1X.sub.2X.sub.3X.sub.4 (I), where X.sub.1 is R, H, or K, X.sub.2 is R, K, D, H, W, Q, Y, or T, X.sub.3 is any amino acid, and X.sub.4 is W, F, or Y; and X.sub.1X.sub.2X.sub.3X.sub.4 (II), where X.sub.1 is R, H, or K, X.sub.2 is any amino acid, X.sub.3 is L, G, I, W, R, M, D, E, A, V, or K, and X.sub.4 is W, F, or Y.

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.

Compounds and compositions are disclosed in which a quaternized drug unit is linked to a targeting ligand unit from which a tertiary amine-containing drug is released at the targeted site of action.

Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease using the compounds and compositions of the invention are also disclosed.

Novel peptides are described which comprise an amino acid motif selected from the group consisting of PG, GP, PI and IG and having up to 10 amino acids upstream and/or downstream of the amino acid motif, wherein P in the motif is proline or hydroxyproline and the peptide stimulates the development, maintenance and repair of bone, cartilage and associated connective tissue.The invention further relates to pharmaceutical compositions of these peptides, as well as therapeutic and prophylactic uses of such peptides.

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.