Occidiofungin is a cyclic nonribosomally synthesized antifungal peptide with submicromolar activity. This invention is directed to compositions enriched for particular occidiofungin diastereomers/conformers, methods of making compositions enriched for particular diastereomers/conformers and microorganisms suitable for producing enriched compositions of particular diastereomers/conformers. Methods of treating fungal infections or plants infected by fungi are also provided.

Occidiofungin is a cyclic nonribosomally synthesized antifungal peptide with submicromolar activity. This invention is directed to compositions enriched for particular occidiofungin diastereomers/conformers, methods of making compositions enriched for particular diastereomers/conformers and microorganisms suitable for producing enriched compositions of particular diastereomers/conformers. Methods of treating fungal infections or plants infected by fungi are also provided.

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.

Molecular scaffolds, including cyclic peptides, that have high (large) cell permeability.

Molecular scaffolds, including cyclic peptides, that have high (large) cell permeability.

The present invention concerns peptides and nucleic acids encoding the peptides, and their use for modulating large conductance Ca.sup.2+ activated K.sup.+ (BK) channel activity in cells; for treating conditions such as presbycusis (age-related hearing loss), audiogenic seizures, alcohol addiction, cancer, and neurodegenerative disease; and for delivering a cargo moiety to the brain of a subject through the blood-brain barrier.

The present invention concerns peptides and nucleic acids encoding the peptides, and their use for modulating large conductance Ca.sup.2+ activated K.sup.+ (BK) channel activity in cells; for treating conditions such as presbycusis (age-related hearing loss), audiogenic seizures, alcohol addiction, cancer, and neurodegenerative disease; and for delivering a cargo moiety to the brain of a subject through the blood-brain barrier.

The present invention provides a cyclic peptide represented by formula (I)

##STR00001##

[wherein A is selected from the ring-forming groups A.sub.1 to A.sub.5; X.sub.aa1 is a residue of an aromatic amino acid; X.sub.aa2 is a residue of an aromatic amino acid, a basic amino acid, or an aliphatic amino acid; X.sub.aa3 and X.sub.aa8 each have a structure independently selected from a residue of an amino acid represented by formula (III) or (III) in which thiol groups of X.sub.aa3 and X.sub.aa8 form a bond; X.sub.aa4 is a residue of a neutral amino acid; X.sub.aa5 is a residue of a basic amino acid; X.sub.aa6 is a residue of a neutral amino acid or an acidic amino acid; X.sub.aa7 is a residue of an aromatic amino acid; X.sub.aa9 is a residue of an aromatic amino acid, an aliphatic amino acid, or a basic amino acid; X.sub.aa10 is a residue of an aromatic amino acid; and X.sub.aa11 is a residue of an aliphatic amino acid], or a pharmaceutically acceptable salt thereof.

The present invention provides a cyclic peptide represented by formula (I)

##STR00001##

[wherein A is selected from the ring-forming groups A.sub.1 to A.sub.5; X.sub.aa1 is a residue of an aromatic amino acid; X.sub.aa2 is a residue of an aromatic amino acid, a basic amino acid, or an aliphatic amino acid; X.sub.aa3 and X.sub.aa8 each have a structure independently selected from a residue of an amino acid represented by formula (III) or (III) in which thiol groups of X.sub.aa3 and X.sub.aa8 form a bond; X.sub.aa4 is a residue of a neutral amino acid; X.sub.aa5 is a residue of a basic amino acid; X.sub.aa6 is a residue of a neutral amino acid or an acidic amino acid; X.sub.aa7 is a residue of an aromatic amino acid; X.sub.aa9 is a residue of an aromatic amino acid, an aliphatic amino acid, or a basic amino acid; X.sub.aa10 is a residue of an aromatic amino acid; and X.sub.aa11 is a residue of an aliphatic amino acid], or a pharmaceutically acceptable salt thereof.