There is provided an α-carbonyl alkenyl ester and a preparation method therefor, and the α-carbonyl alkenyl ester is further used to react with a primary or secondary amine to prepare an amide. The two reactions are combined to develop an amide bond and peptide bond formation method that directly use carboxylic acids and amines as starting materials and allenones as a condensing reagent. The α-carbonyl alkenyl ester corresponding to an α-amino acid serves as a peptide synthesis building block and is used in solid phase peptide synthesis. The method is carried out under mild reaction conditions, simple to operate, and has a high yield. Compared with existing amide bond condensation reagents, the allenones have the advantages of being simple to prepare, having good stability, a low molecular weight, not racemizing when activating α-chiral carboxylic acids, and is a novel amide bond and peptide bond condensing reagent.

The disclosure provides proteasome inhibitors that can be used to halt cell division of rapidly dividing cells by preventing the degradation of cell cycle-regulating proteins, such as cyclins, cyclin-dependent kinase inhibitors, and p53. The proteasome inhibitor compounds can be used to inhibit the proliferation of cancer cells.

Methods of treating aging related skin changes and of increasing skin thickness with topical administration of N-acyldipeptide derivatives are described. Compositions comprising 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.

Provided is a method of preparing an N-acetyl dipeptide and an N-acetyl amino acid, the method including producing the N-acetyl dipeptide and the N-acetyl amino acid by reaction of an amino acid with acetic anhydride or acetyl chloride.

The present invention is related to the use of HMGB1 antagonists such as K883 in the treatment and/or prevention and/or inhibition of severe sepsis in mammals, e.g., humans, and pharmaceutical compositions for the same comprising HMGB1 antagonists in an effective amount to treat and/or prevent and/or inhibit this condition.

The present disclosure relates to a pair of flanking sequences for a split intein wherein, the pair of flanking sequences comprises: a flanking sequence a and a flanking sequence b; the flanking sequence a is located at the N-terminus of the split intein N-terminal protein splicing region (In), and is between the N-terminal extein (En) and the In; the flanking sequence b is located at the C-terminus of the split intein C-terminal protein splicing region (Ic), and is between the Ic and the C-terminal extein (Ec); and the split intein is NpuDnaE.

The present invention is related to HMGB1 antagonists and, in particular, HMGB1 tetramer peptidomimetics which have been stabilized with at least one azatide linkage, such as K883. The present invention is also related to pharmaceutical compositions comprising HMGB1 antagonists such as K883.

Disclosed are a mild and efficient preparation method for an α-acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The α-acyloxyenamide compound is obtained by an addition reaction of a ynamide and a carboxylic acid in dichloromethane under conditions where the temperature is 0° C. to 50° C.; the produced α-acyloxyenamide compound can react with an amine compound to produce an amide or a polypeptide; the two reactions can be carried out step by step, and can also be carried out in one pot. According to the invention, the reaction conditions are mild and no metal catalyst is required; when the carboxylic acid, which has chirality on an alpha site of carboxyl, forms an amide bond or a peptide bond, no racemization occurs; and the operation is simple and the application range is wide.

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.

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.