Abstract: A method for identifying host genes and encoded proteins for potential targets for therapeutic intervention employs a Gene Search Vector that is either lentivirus or MMLV-based, and can be used to interrogate an entire cell genome without prior knowledge of the genomic sequence. This Random Homozygous Gene Perturbation (RUGP) technique is rapidly verifiable and is used to identify potential host targets for intervention for influenza, HIV and other viral infections. Using Thermal Assymetric Interlaced (TAIL)-PCR, the period for identification of promising targets is reduced from months to weeks or less. Specific targets including PTCH1, Robo1 and Nedd4 are reviewed in detail.

Abstract: A method for identifying host genes and encoded proteins for potential targets for therapeutic intervention employs a Gene Search Vector that is either lentivirus or MMLV-based, and can be used to interrogate an entire cell genome without prior knowledge of the genomic sequence. This Random Homozygous Gene Perturbation (RUGP) technique is rapidly verifiable and is used to identify potential host targets for intervention for influenza, HIV and other viral infections. Using Thermal Assymetric Interlaced (TAIL)-PCR, the period for identification of promising targets is reduced from months to weeks or less. Specific targets including PTCH1, Robo1 and Nedd4 are reviewed in detail.

Abstract: XMRV appears to be related to both prostate cancer if it infects a male germ cell and chronic fatigue syndrome in both sexes. (If the virus does not infect a germ cell). Prostate cancer cells exhibit TSG101 on the surface only upon infection with a virus like XMRV. Antibodies to TSG101 can be effective diagnostics to identify individuals with a predisposition to prostate. They can also be used in place of current diagnostics to confirm the presence of prostate cancer. TSG101 antibodies, when administered in vivo, exhibit the ability to reduce tumor size, suppress metastatic transformation and extend survival.

Abstract: A method for identifying host genes and encoded proteins for potential targets for therapeutic intervention employs a Gene Search Vector that is either lentivirus or MMLV-based, and can be used to interrogate an entire cell genome without prior knowledge of the genomic sequence. This Random Homozygous Gene Perturbation (RUGP) technique is rapidly verifiable and is used to identify potential host targets for intervention for influenza, HIV and other viral infections. Using Thermal Assymetric Interlaced (TAIL)-PCR, the period for identification of promising targets is reduced from months to weeks or less. Specific targets including PTCH1, Robo1 and Nedd4 are reviewed in detail.

Abstract: The preparation of macrocyclic molecules from linear, synthetic thioester precursors is disclosed. An excised thioesterase domain isolated from either a polyketide synthases (PKS) or non-ribosomal peptide synthetases (NRPS) multido system catalyzes the cyclization reaction. Thioester substrates also are described that are efficiently cyclized by the method of the present invention. Additionally, macrocyclic molecules, including macrolactones and macrolactams, that are prepared by the macrocyclization methods of the invention are described.

Abstract: The invention features a new solid supports having at least one amino functionality and a linker bound to the solid support through at least a portion of the amino functional groups. The invention also features solid support bound substrates suitable for use in the formation of macrocycles by a TE domain catalyzed macrocyclization reaction. The invention features methods of making the solid supports and solid support bound substrates of the invention and methods of effecting macrocyclizations of solid support bound substrates. The invention further provides new macrocyclic molecules having one or more peptide domains and one or more polyketide domains in the macrocyclic ring. In another embodiment of the invention, libraries of macrocycles are provided as well as methods of forming libraries of macrocycles from libraries of solid support bound substrates are provided.

Abstract: The preparation of macrocyclic molecules from linear, synthetic thioester precursors is disclosed. An excised thioesterase domain isolated from either a PKS or NRPS multidomain system catalyzes the cyclization reaction. Thioester substrates also are described that are efficiently cyclized by the method of the present invention. Additionally, macrocyclic molecules, including macrolactones and macrolactams, that are prepared by the macrocyclization methods of the invention are described.