Disclosed are a mild and efficient preparation method for an -acyloxyenamide compound and a use thereof in the synthesis of an amide and a polypeptide. The -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 -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.

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 are modified lipid compounds and their use in the formation of lipid assemblies. Also provided are lipid assemblies including (a) an amphoteric lipid including in covalent association with (i) one or more acyl chains; (ii) one or more weak base moiety; (iii) one or more weak acid moiety; the lipid assembly also including (b) one or more additional lipids, at least one of which being a zwitterionic lipid. In some embodiments, the amphoteric lipid is a compound including (a) a tri-functional moiety; (b) two non-phosphate lipid chains associated with two of the functional moieties of said tri-functional moiety; (c) optionally a spacer moiety associated with the third of the functional moieties of said tri-functional moiety; and (d) a polyalkylamine optionally including a short peptide with one to several carboxylic acid residues. Further provided are the uses of the lipid assembly, inter alia, for transfection or cancer treatment.

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.

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.

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.

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.

The compounds of the present invention are represented by the following compounds having Formula (I) where the substituents R.sup.1-R.sup.10, X, Y, k, m, n, q, and s are as defined herein. These compounds are used in the treatment of cancer, immunologic disorders, autoimmune disorders, neurodegenerative disorders, or inflammatory disorders or for providing immunosuppression for transplanted organs or tissues.

Compositions of foods, vitamin and mineral supplements, topical or oral drugs, and cosmetic products containing a small peptide or peptides for slowing degradation, for example by transition metals. The peptides are di, tri, terra-, and/or penta-peptides containing two or more aspartic acid residues. The degradation of several of the vitamin and other constituents vitamin-mineral supplements can be considerably slowed by composition incorporating such peptides, particularly if soluble (and thus bioavailable) forms of copper and/or iron are also present. The peptides can be hydrolyzed by the normal digestive process thus releasing bound metals. Multiple aspartate peptide(s) compositions with foods, topical or oral drugs, cosmetic, and hair care products can replace synthetic chelating preservative agents. Methods are also described to effectively slow degradation and preserve the above products using multiple aspartate peptides.

The compounds of the present invention are represented by the following compounds having Formula I and Formula (I):

##STR00001##

where the substituents R.sup.1, R.sup.2, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R, R, X, Y, and Z are as defined herein and

##STR00002##

where the substituents R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R, R, X, Y, and Z are as defined herein. These compounds are used in the treatment of bacterial infections, parasite infections, fungal infections, cancer, immunologic disorders, autoimmune disorders, neurodegenerative diseases and disorders, inflammatory disorders, or muscular dystrophy or for providing immunosuppression for transplanted organs or tissues.