The disclosure is related to a method of treating a disorder, such as Prader Willi Syndrome (PWS), obesity or hyperphagia, in a subject using a melanocortin-4 receptor (MC4R) agonist. Also described is method of treating a subject having a deficiency in the pro-opiomelanocortin (POMC)-MC4R pathway, such as a POMC-null or a PC SK-null subject, using a MC4R agonist.

The disclosure is related to a method of treating a disorder, such as Prader Willi Syndrome (PWS), obesity or hyperphagia, in a subject using a melanocortin-4 receptor (MC4R) agonist. Also described is method of treating a subject having a deficiency in the pro-opiomelanocortin (POMC)-MC4R pathway, such as a POMC-null or a PC SK-null subject, using a MC4R agonist.

There is described herein use of a compound of formula (I) below to make cyclic peptides. ##STR00001##

There is described herein use of a compound of formula (I) below to make cyclic peptides. ##STR00001##

Methods and uses for treating cancer in a subject are provided. In particular, the present disclosure provides methods and uses relating to treating a subject with cancer by activating human mitochondrial CIpP (HsCIpP). The present disclosure further provides methods and uses of an acyldepsipeptide (ADEP) analog that activates HsCIpP in the subject in need thereof.

Methods and uses for treating cancer in a subject are provided. In particular, the present disclosure provides methods and uses relating to treating a subject with cancer by activating human mitochondrial CIpP (HsCIpP). The present disclosure further provides methods and uses of an acyldepsipeptide (ADEP) analog that activates HsCIpP in the subject in need thereof.

Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Recombinant and in vitro reconstitution methods for producing lasso peptides are provided. Methods of screening lasso peptides are also provided.

There is described herein use of a compound of formula (I) below to make cyclic peptides. ##STR00001##