The invention relates to macrocyclic peptides and pharmaceutical compositions thereof. The invention further relates to pharmaceutical compositions for modulating opioid receptor activity.

Disclosed are compounds having enhanced potency in the modulation of NMDA receptor activity. Such compounds are contemplated for use in the treatment of diseases and disorders, such as learning, cognitive activities, and analgesia, particularly in alleviating and/or reducing neuropathic pain. Orally available formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

Provided herein is a cyclic tetrapeptides including alternating - and 3-amino acids and metal complexes thereof. The cyclic tetrapeptides are useful for coordinating a metal selected from Pb, Cd, Hg and As. Also provided herein is the use of the cyclic tetrapeptides in treating a disease, particularly metal poisoning, and the use in remediation of contaminated water and soil. Also provided herein are methods for detecting said metals in various substrates are provided.

Described are dual mass-spectrometry-cleavable cross-linkers that can be cleaved selectively using two differential tandem mass-spectrometric techniques such as collision induced dissociation (CID) or electron transfer dissociation (ETD), i.e., a dual cleavable crosslinking technology (DUCCT) cross-linker. When used to cross-link a macromolecule, such as a peptide, MS/MS fragmentation produces two signature complementary mass spectra of same cross-linked peptides, the analysis of which gives rise to high confidence in characterizing the structures of the cross-linked macromolecules as well as sites of interactions. Also described, are methods of making and using DUCCT cross-linkers.

The disclosure relates to macrocyclic peptides and pharmaceutical compositions thereof. The disclosure further relates to pharmaceutical compositions for modulating opioid receptor activity. The macrocyclic tetrapeptides provided herein are useful in treating diseases or disorders relating to the activity of one or more opioid receptors, such as neurological disorders.

The invention relates to a method for inhibiting an ADAM protease, comprising inhibiting binding to an integrin-binding loop of a disintegrin domain in the ADAM protease. Also provided are cyclic peptides which inhibit binding to an integrin-binding loop of an ADAM protease, as well as associated pharmaceutical compositions, uses and methods of treatment.

The present invention provides methods of making 47 peptide monomer and dimer antagonists. Methods of the present invention include solid phase and solution phase methods, as well as synthesis via condensation of smaller peptide fragments. Methods of the present invention further include methods directed to the synthesis of peptides comprising one or more penicillamine residues.

Macrocyclization of amino acids or linear peptides upon reaction with amphoteric amino aldehydes and isocyanides is provided.

The instant invention describes macrocyclic compounds having therapeutic activity, and the mechanism and methods of treating disorders such as autoimmune diseases, inflammation, and cancer, tumors and cell proliferation related disorders.

Cyclic tetrapeptide stereochemical isomers of CJ-15,208, pharmaceutical compositions from such cyclic tetrapeptides, and methods of using such pharmaceutical compositions. The cyclic tetrapeptide compounds and pharmaceutical compositions disclosed herein are potent analgesics active in several pain models with generally minimal tolerance and reduced likelihood to induce addiction relative to other known opiates.