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.

Disclosed are peptides having the structure according to formula (Ia) or (Ib) or (II): wherein NH-Q-C(O) is a peptide chain optionally comprising an amino acid residue having a sidechain covalently bonded to Z.sub.2; Z.sub.1 is a moiety comprising an aromatic group, a therapeutic agent, a fluorophore, or a nanoparticle; Z.sub.2 is H, a therapeutic agent, a fluorophore, or a nanoparticle; and J, if present (as in Ib or II), is a linker between the peptide chain and the thiophosphate group or thioester group. Also disclosed are pharmaceutical compositions that contain a peptide, as well as dephosphorylated peptides of the invention, which may take one or more forms include a nanofiber or a supramolecular hydrogel. Use of the peptides for delivering a therapeutic agent or drug moiety into the Golgi apparatus, imaging a cell, treating a patient having a cancerous condition, treating a patient having Alzheimer's or Parkinson's disease are also disclosed.

A 3D structure of a hydrogel for supporting cell growth or for use in sustained drug delivery is formed using peptides and/or peptide derivatives that self-assemble via cross-linking into a stiff gel. The hydrogel structure is formed using a method based on 3D printing. A hydrogel precursor is extruded under conditions to generate a hydrogel, by extruding a solution of the peptides into a solution containing cations, whereby the cations enable cross-linking of pi-stacked peptides, or by co-extruding it with the cations, the peptides and cations being mixed only at the point of co-extrusion. The stiffness of the hydrogel can be tuned by adjusting the combination of peptides, either by the selection of peptides or combinations thereof, or the proportions of the combinations, and/or by adjusting the proportion of cations present.

Disclosed herein are fibrillar molecular aggregates, which are morphologically and phenotypically similar to oligomers of aberrant proteins. The molecular aggregates, formed by self-assembly of small hydrophobic molecules, prevent the growth of microtubules. This unprecedented mechanism of self-assembly to interfere with self-organization allows inhibition of the growth of cancer cells.

Novel compounds of N-Lipoic-amino acid, N-Lipoic-peptides and their derivatives are described. Also described are compositions and method of compositions containing the derivatives of the amino acids or peptides, and their uses including treating and preventing dermatological or cosmetic conditions or other disorders of the cutaneous system. Compositions and methods of using the compositions for skin lightening and cosmetics are also disclosed.

The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.

This disclosure relates to isotopically modified amino acids and their pharmaceutical or nutritional uses in stabilizing pharmaceutical protein-based formulations, proteins with long life span, and preventing or treating disease such as Alzheimer's disease. Specifically, the disclosure provides protein drugs having increased stability comprising an L-aspartate (L-Asp) residue or an L-asparagine (L-Asn) residue, wherein the L-Asp residue or the L-Asn residue comprises a deuterium atom.

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 invention provides novel compounds having the general formula (I)

##STR00001##

wherein R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.3, R.sup.8, R.sup.10, R.sup.11 and R.sup.23 are as described herein, compositions including the compounds and methods of using the compounds.

The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.