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.

The present invention is directed to somatostatin receptor antagonist compounds having the structure of Formula I, compositions comprising the same, and methods of using such compounds and compositions. The compounds may be useful in the prevention or treatment of hypoglycemia. ##STR00001##

The invention relates to improvements in drug delivery and to the use of Cell Penetrating Agents (CPA's) or Cell Penetrating Peptides (CPP's) which have been stabilized by, for example: i) stapling two amino acids to form Stapled CPP's (StaP's) or ii) stitching three or more amino acids to form stitched CPP's (StiP's). More particularly there is provided a drug carrying cell penetrating molecule (DCCPM) comprising: a biologically active compound (BAC), and a cell penetrating agent (CPA), which BAC and CPA are linked directly or via a bi-functional linker (BFL). The CPA is a stabilized peptide (CPP) which has a conformation imposed upon it by stapling to form a stapled peptide (StaP) or stitching to form a stitched peptide (StiP). The StiP or StaP comprise a cross link or bridge between at least two amino acids of the peptide and the cross link or bridge provides a cyclisation between at least two amino acids which are not formed by an olefin metathesis. Cyclisation may be achieved by one or more of: condensation of an aldehyde or ketone with a hydrazine or protected hydrazine; a thiol-ene Michael addition; a di-sulfide formation; a Huisgen 1,3 di-polar cycloaddition; a reaction between an amine and carboxylic acid; a singlet or triplet based carbine reaction; or a Suzuki or Sonogashira coupling.

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.

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.

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.

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.

The present invention relates to heterotandem bicyclic peptide complexes which comprise a first peptide ligand, which binds to a component present on an immune cell, conjugated via a linker to a second peptide ligand, which binds to a component present on a cancer cell. The invention also relates to the use of said heterotandem bicyclic peptide complexes in preventing, suppressing or treating cancer.

The present invention relates to heterotandem bicyclic peptide complexes which comprise a first peptide ligand, which binds to a component present on an immune cell, conjugated via a linker to a second peptide ligand, which binds to a component present on a cancer cell. The invention also relates to the use of said heterotandem bicyclic peptide complexes in preventing, suppressing or treating cancer.

Disclosed herein are compositions and methods suitable for treating acute leukemia by inhibiting π π π stacking in the YEATS protein domain. YEATS protein domains are typically found in a variety of chromatin modification molecular complexes. Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs. Quantitative analysis of the inhibitory activity of YEATS domain inhibitors by use of a fluorescence-based assay revealed that several of the tested inhibitors achieved 50% inhibition at the submicro/nanomolar level. As such, provided is the use of small molecule inhibitors that target the ENL YEATS domain to selectively kill leukemic MLL-r cells.