The disclosure provides for peptide-based bolaamphiphile vectors that are capable of encapsulating a variety of agents, including peptides, proteins, nucleic acids, and drugs. The disclosure further provides for delivering these agents across biological membranes using the peptide-based bolaamphiphile vectors.

Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging.

Compounds for targeting and agents for imaging, prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging.

Compositions of dendrimers conjugated with one or more glutamine antagonist(s) that inhibit glutamine metabolism, preferably in activated microglia, and methods of use thereof for treating, alleviating, and/or preventing one or more neurological, oncological, and/or immune disorders associated with pathogenic or dysregulated glutamine-dependent pathways and/or glutamate transmission, have been developed. Dendrimers conjugated with one or more glutamine antagonists effectively inhibit the activity of glutaminase without any systemic toxicity. Dendrimers conjugated with one or more glutamine antagonists accumulate in activated microglia associated with the injured or diseased cells and tissues.

A compound of formula (I) or a pharmaceutically acceptable derivative thereof, (formula 1) wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, m and n are defined in the specification; a process for preparing such compounds; a pharmaceutical composition comprising such compounds; and the use of such compounds in medicine.

##STR00001##

The present invention provides compounds of Formula (I) and (II):

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.4, R.sup.5, R.sup.6, X and n are as defined herein, and wherein R.sup.3 is hydrogen or a sulfur protecting group. Compounds of Formula (I) and (II), wherein R.sup.3 is hydrogen, may be useful in methods for detecting a reactive metabolite in a sample, e.g., wherein the metabolite is generated from the metabolism of a test compound, and wherein the metabolite and the compound of Formula (I) or (II) react to form a detectable adduct, e.g., detectable by mass spectrometry.

A method for producing -Glu-Val-Gly comprising the step of reacting Val-Gly with a -glutamyl group donor in the presence of a -glutamyltransferase, a microorganism containing the enzyme, or a processed product thereof to generate -Glu-Val-Gly, wherein the -glutamyltransferase consists of a large subunit and a small subunit, and the small subunit has a specific mutation.

Disclosed herein is pyrroline-carboxy-lysine (PCL), a pyrrolysine analog, which is a natural, biosynthetically generated amino acid, and methods for biosynthetically generating PCL. Also disclosed herein are proteins, polypeptides and peptides that have PCL incorporated therein and methods for incorporating PCL into such proteins, polypeptides and peptides. Also disclosed herein is the site-specific derivatization of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein. Also disclosed herein is the crosslinking of proteins, polypeptides and peptides having PCL or pyrrolysine incorporated therein.

The present disclosure provides methods and reagents useful for analyzing protein-protein interfaces such as interfaces between a presenter protein (e.g., a member of the FKBP family, a member of the cyclophilin family, or PIN1) and a target protein. In some embodiments, the target and/or presenter proteins are intracellular proteins. In some embodiments, the target and/or presenter proteins are mammalian proteins.

Macrocyclic compounds that specifically inhibit insulin degrading enzyme (IDE) are provided. Pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, polymorphs, tautomers, isotopically enriched forms, and prodrugs of the macrocyclic IDE inhibitors are also described. Pharmaceutical compositions are also provided. In vivo and in vitro methods of using the IDE inhibitor, and pharmaceutical compositions comprising the IDE inhibitor, for example, for the inhibition of IDE in a subject exhibiting aberrant IDE activity, impaired insulin signaling, or insulin resistance, for example, a subject having diabetes, are also provided.