Disclosed are peptidomimetic macrocycles comprising a helix, such as an alpha helix, and methods of using such macrocycles for the treatment of disease such as cancer. In other aspects, the peptidomimetic macrocycle comprises an α,α-disubstituted amino acid, or may comprise a crosslinker linking the α-positions of at least two amino acids or at least one of said two amino acids may be an α,α-disubstituted amino acid. Further included is the targeting of components of the Wnt signaling pathway such as the Tcf4-/3-catenin complex.

The present disclosure provides macrocyclic and macrobicyclic peptides with secondary structures that are stabilized over the corresponding non-cyclic peptides. The macrocyclic and macrobicyclic peptides are formed from peptides with adduct-forming, complementary reactive side chain moieties.

The present disclosure provides macrocyclic and macrobicyclic peptides with secondary structures that are stabilized over the corresponding non-cyclic peptides. The macrocyclic and macrobicyclic peptides are formed from peptides with adduct-forming, complementary reactive side chain moieties.

The invention features echinocandin class compounds. The compounds can be useful for the treatment of fungal infections.

Disclosed is a general, reversible bicyclization strategy to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell-permeable bicyclic peptidyl inhibitor against the NEMO-IKK interaction.

Disclosed is a general, reversible bicyclization strategy to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell-permeable bicyclic peptidyl inhibitor against the NEMO-IKK interaction.

A peptide or salt thereof includes an amino acid sequence set forth in SEQ ID NO:1 containing an amino acid sequence in which at least one of (a) the first aspartate residue and the second aspartate residue from the N-terminus, or (b) the 17th glycine residue and the 18th aspartate residue from the N-terminus is deleted. A peptide or salt thereof includes an amino acid sequence set forth in SEQ ID NO:5 containing an amino acid sequence in which the sixth aspartate residue from the N-terminus is substituted with another amino acid residue. The peptides or salts thereof include three specific serine residues of which at least two serine residues are phosphorylated, and have an action of inhibiting biotissue calcification.

A peptide or salt thereof includes an amino acid sequence set forth in SEQ ID NO:1 containing an amino acid sequence in which at least one of (a) the first aspartate residue and the second aspartate residue from the N-terminus, or (b) the 17th glycine residue and the 18th aspartate residue from the N-terminus is deleted. A peptide or salt thereof includes an amino acid sequence set forth in SEQ ID NO:5 containing an amino acid sequence in which the sixth aspartate residue from the N-terminus is substituted with another amino acid residue. The peptides or salts thereof include three specific serine residues of which at least two serine residues are phosphorylated, and have an action of inhibiting biotissue calcification.

The present disclosure provides a large combinatorial library of cell-permeable bicyclic peptides. The bicyclic peptides described herein include the first ring consisted of randomized peptide sequences for potential binding to a target of interest while the second ring featured a family of different cell-penetrating motifs, for both cell penetration and target binding. The library was screened against the IκB kinase α/β (IKKα/β)-binding domain of NF-κB essential modulator (NEMO), resulting in the discovery of several cell-permeable bicyclic peptides which inhibited the NEMO-IKKβ interaction, thereby selectively inhibiting canonical NF-κB signaling in mammalian cells and the proliferation of cisplatin-resistant ovarian cancer cells.

The present invention relates to antibodies, or antigen-binding fragments thereof, directed against human leukocyte antigen-G (HLA-G) protein and raised against an immunogenic peptide derived from the α3 domain of HLA-G protein. The invention further relates to the immunogenic peptide, and methods for producing said anti-HLA-G specific antibodies.