Abstract: The present invention provides compositions and methods for inducing DNA breaks in specifically-targeted cells, in particular cancer and HIV-infected cells, thereby promoting cell death.

Abstract: Isolated peptides comprising sequences derived from the protein integrase of HIV-1, as well as their analogs, mixtures, conjugates with permeability enhancing moieties, and pharmaceutical compositions are disclosed. The peptides and compositions are capable of selectively killing HIV-1 infected cells and are used in treatment of HIV infection and AIDS.

Abstract: Isolated peptides comprising sequences derived from the protein integrase of HIV-1, as well as their analogs, mixtures, conjugates with permeability enhancing moieties, and pharmaceutical compositions are disclosed. The peptides and compositions are capable of selectively killing HIV-1 infected cells and are used in treatment of HIV infection and AIDS.

Abstract: Isolated peptides comprising sequences derived from the protein integrase of HIV-1, as well as their analogs, mixtures, conjugates with permeability enhancing moieties, and pharmaceutical compositions are disclosed. The peptides and compositions are capable of selectively killing HIV-1 infected cells and are used in treatment of HIV infection and AIDS.

Abstract: Isolated peptides comprising sequences derived from the protein integrase of HIV-1, as well as their analogs, mixtures, conjugates with permeability enhancing moieties, and pharmaceutical compositions are disclosed. The peptides and compositions are capable of selectively killing HIV-1 infected cells and are used in treatment of HIV infection and AIDS.

Abstract: The present invention relates to a substance that specifically binds a nuclear localization signal (NLS)-containing molecule. Said substance may be a naturally occurring, synthetic or recombinant antibody, or it may be a protein, a peptide or a small molecule. Preferably, said NLS-containing molecule is a HIV-1 protein, more preferably Vpr or Tat. In addition, the present invention relates to a composition or a vaccine comprising the substance of the invention, as well as methods of inhibiting viral infection through the administration thereof.

Abstract: A conjugate of a histone moiety covalently attached to a macromolecule-of-interest, in which the histone moiety is transportable through the cell membrane and importable into the cell nuclei, is disclosed. Further disclosed are chemical and recombinant methods of preparing such a conjugate, pharmaceutical compositions containing same and uses thereof for delivering therapeutically active macromolecules into cells. A novel method for quantitatively determining a cytoplasmic uptake and/or a nuclear uptake of a moiety into cells is also disclosed.

Abstract: The present invention is concerned with new delivery systems for intracellular and intranuclear import of desired constituents based on dermaseptin-derived peptides. For that purpose, the present invention provides a chimeric molecule, comprising a dermaseptin-derived peptide and at least one biologically or pharmaceutically active constituent. The chimeric molecule of the invention may further comprise a peptide having nuclear localization signal (NLS)-like properties. In addition, a fusion peptide is provided, consisting of a dermaseptin-derived peptide and a peptide with NLS-like properties. The present invention also provides compositions and systems for the intracellular delivery of active constituents, and methods for screening cell-permeable nuclear import inhibitors and for detecting changes in intracellular levels of proteins and nucleic acids.

Abstract: The design and the synthesis of backbone cyclic peptide analogs which functionally mimic the nuclear localization signal (NLS) region of macromolecules is disclosed. The principles of the invention are exemplified for the NLS sequences of the human immunodeficiency virus type 1 proteins MA, Vpr, Tat and NLS-like sequences of HIV-1 protein Vif. We disclose the discovery of a novel, highly potent backbone cyclic peptide, designated BCvir, which inhibits nuclear import with an IC50 value of 35 nM. This inhibitory potency is to be compared to 12 &mgr;M exhibited by the linear parent HIV-1 MA NLS peptide. BCvir also reduced HIV-1 production by 75% in infected non-dividing cultured human T-cells and was relatively resistant to tryptic digestion. These properties render backbone cyclic peptide analogs of NLS or NLS-like sequences as candidates for novel drugs based on blocking nuclear import of viral genomes.