Louisiana State University and Agricultural & Mechanical College

Agricultural and Mechanical College

William Hansel

Jesse M Jaynes

Frederick M Enright

Philip H Elzer

Patricia A Melrose

Lane D Foil

Wen H Yu

Samuel M McCann

Jeong-Mook Lim

Kenneth L Koonce

Robert P Hammer

Sita Aggarwal

Samuel M Mccann

Frederick Enright

Conjugating LHRH to(LHRH-) substantially enhances the bioavailability of, targets it to cells expressing LHRH receptors, facilitates intravenous administration, and increases the anti-cancer efficacy of. The conjugate may be used against cancer cells that express the LHRH receptor: pancreas, prostate, breast, testicular, uterine, ovarian, melanoma. LH-conjugates may be used against cancer cells that express the LH receptor: prostate, breast, ovary, testis, uterus, pancreas, and melanoma.

Curcumin conjugates for treating and preventing cancers

Conjugating LHRH to curcumin (LHRH-Curcumin) substantially enhances the bioavailability of curcumin, targets it to cells expressing LHRH receptors, facilitates intravenous administration, and increases the anti-cancer efficacy of curcumin. The conjugate may be used against cancer cells that express the LHRH receptor: pancreas, prostate, breast, testicular, uterine, ovarian, melanoma. LH-Curcumin conjugates may be used against cancer cells that express the LH receptor: prostate, breast, ovary, testis, uterus, pancreas, and melanoma.

Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid. The two components&#x2014;the ligand and the lytic peptide&#x2014;may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide. The compounds may be used in gene therapy to treat malignant or non-malignant tumors, and other diseases caused by clones or populations of 'normal' host cells bearing specific receptors (such as lymphocytes), because genes encoding a lytic peptide or encoding a lytic peptide/peptide hormone fusion may readily be inserted into hematopoietic stem cells or myeloid precursor cells.

Ligand/lytic peptide methods of use

Genes encoding hormone and lytic peptides

Nitric oxide adversely affects survival and development of cells such as oocytes and embryos in vitro, particularly in a co-culture system. The addition of a nitric oxide inhibitor such as hemoglobin to such systems eliminates this toxic effect, and promotes mammalian oocytes, embryos, or other cells in vitro.

Nitric oxide-scavenging system for culturing oocytes, embryos, or other cells

Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to induce sterility or long-term contraception in mammals. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in mammals in vivo. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) The two components&mdash;the ligand and the lytic peptide&mdash;may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide.

Compositions and methods for contraception in or sterilization of mammals

Amphipathic lytic peptides are ideally suited to use in a ligand/cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce sterility or long-term contraception, or to attack tumor cells, or to selectively lyse virally-infected cells, or to attack lymphocytes responsible for autoimmune diseases. The peptides act directly on cell membranes, and need not be internalized. Administering a combination of gonadotropin-releasing hormone (GnRH) (or a GnRH agonist) and a membrane-active lytic peptide produces long-term contraception or sterilization in animals in vivo. Administering in vivo a combination of a ligand and a membrane-active lytic peptide kills cells with a receptor for the ligand. The compounds are relatively small, and are not antigenic. Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.) Lysis of tumor cells is rapid. The two components&mdash;the ligand and the lytic peptide&mdash;may optionally be administered as a fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to lysis by the lytic peptide. The compounds may be used in gene therapy to treat malignant or non-malignant tumors, and other diseases caused by clones or populations of &ldquo;normal&rdquo; host cells bearing specific receptors (such as lymphocytes), because genes encoding a lytic peptide or encoding a lytic peptide/peptide hormone fusion may readily be inserted into hematopoietic stem cells or myeloid precursor cells.

Growing community of inventors

Baton Rouge, LA, United States of America

William Hansel