Abstract: An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. in vitro assays for discovering agents which effect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative and hyperproliferative disorders are provided.

Abstract: The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a novel family of cell-cycle regulatory proteins (“CCR-proteins”). As described herein, this family of proteins includes a polypeptide having an apparent molecular weight of 16 kDa, and a polypeptide having an apparent molecular weight of approximately 15 kDa, each of which can function as an inhibitor of cell-cycle progression, and therefore ultimately of cell growth. Thus, similar to the role of p21 to the p53 checkpoint, the subject CCR-proteins may function coordinately with the cell-cycle regulatory protein, retinoblastoma (RB). Furthermore, the CCR-protein family includes a protein having an apparent molecular weight of 13.5 kDa (hereinafter “p13.5”). The presumptive role of p13.5, like p16 and p15, is in the regulation of the cell-cycle.

Abstract: A hedgehog conjugate which is characterized in that it contains: a) a polypeptide composed of 10 to 30 hydrophobic amino acids and/or amino acids which form transmembrane helices and are positively charged, b) 1 to 4 aliphatic, saturated or unsaturated hydrocarbon residues with a chain length of 10 to 24 C atoms and with a hydrophobic action or c) a hydrophobic thio compound covalently bound to a hedgehog protein and which has a several-fold increased activity and is suitable as a pharmaceutical agent.

Abstract: The present invention relates to rapid, reliable and effective assays for screening and identifying pharmaceutically effective compounds that specifically inhibit the biological activity of fungal GTPase proteins, particularly GTPases involved in cell wall integrity, hyphael formation, and/or other cellular functions critical to pathogenesis. Another aspect of the present invention relates to novel Candida genes and gene products.

Abstract: Compound of formula (I) wherein: A is a bicyclic heteroaryl, optionally substituted with one or more substituents; B is linker group connecting group A to group D and comprising a 3 or 4 atom linker where each atom is independently selected from carbon, oxygen, nitrogen and sulphur and is optionally subsituted with one or more C1-6 alkyl groups or two of such adjacent alkyl substituents may form a ring; C is aryl or a mono or bicyclic heteroaryl, each of which can be optionally substituted; D is an aryl or heteroaryl, both of which are optionally substituted R1 is hydrogen, C1-5 alkyl, C1-3 alkanoyl or C1-3 alkoxycarbonyl; R2 to R5 are each independently selected from hydrogen, C1-6 alkyl, aryl and heteroaryl containing up to 2 heteroatoms chosen from oxygen, sulphur and nitrogen, the aryl and heteroaryl optionally substituted with C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C1-4 alkanoyl, C1-6 alkylamino, C1-4alkylC1-6alkyoxyl, C1-6alkylaminoC1-6alkyl, nitro, cyano, halogeno, trifl

Abstract: The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein comprising contacting a cell sensitive to the hedgehog protein with a steroidal alkaloid, or other small molecule, in a sufficient amount to reduce the sensitivity of the cell to the hedgehog protein.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here signalin-related genes, which are involved in signal transduction induced by members of the TGF&bgr; superfamily. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: Methods for isolating patched genes, particularly mammalian patched genes, including the mouse and human patched genes, as well as invertebrate patched genes and sequences, are provided. Decreased expression of patched is associated with the occurrence of human cancers, particularly basal cell carcinomas of the skin. The cancers may be familial, having as a component of risk an inherited genetic predisposition, or may be sporadic. The patched and hedgehog genes are useful: in creating transgenic animal models for these human cancers. The patched nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated 15 physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like.

Abstract: The present invention relates to compositions and methods for inhibiting fungal growth. In particular, the present invention relates to methods for use as anti-fungal agents of inhibitors, and compositions thereof, of fungal GGPTase. The inhibitors of fungal GGPTase may be peptides, peptidomimetics, or non-peptides.

Abstract: One aspect of the present invention is the synthesis of a binary method that combines variegated peptide display libraries, e.g., in a “display mode”, with soluble secreted peptide libraries, e.g., in a “secretion mode”, to yield a method for the efficient isolation of peptides having a desired biological activity.

Abstract: The invention relates to methods of preparing plasmid pools by growing colonies in discrete wells of a semi-solid or gelatinous medium. This method may facilitate colony collection, reduce colony overgrowth, reduce contamination by adventitious microorganisms, and increase the efficiency of plasmid screening techniques.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by embryonic patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. In vitro assays for discovering agents which affect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative disorders are provided.

Abstract: The present invention relates to a selection method that allows fast recovery and identification of functional gene fragments which selectively inhibit growth, e.g., are cytostatic or cytotoxic, of particular cell-types, such as transformed cells. The strategy relies, in part, on the ability of small gene fragments to encode dominant-acting synthetic genetic elements (SGEs), e.g., molecules which interfere with the function of genes from which they are derived. SGEs which can be identified by the subject method include, but are not limited to, inhibitory antisense RNA molecules, ribozymes, nucleic acid decoys, and small peptides.

Abstract: The present invention relates to a substantially pure population of viable pancreatic progenitor cells, and methods for isolating such cells. The present invention further concerns certain therapeutic uses for such progenitor cells, and their progeny.

Abstract: The subject invention is directed to the discovery of a protein involved in regulation of cell-cycle progression, and includes reagents and methods related thereto.

Abstract: The present invention relates to the discovery of a new member of the hedgehog receptor family, referred to herein as human ptc-2 (for patched-2 protein). The human ptc-2 polypeptides of the present invention include polypeptides which bind the products of the hedgehog gene family. Hedgehog family members are known for their broad involvement in the formation and maintenance of ordered spatial arrangements of differentiated tissues in vertebrates, both adult and embryonic, and can be used to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

Abstract: The present invention makes available methods and reagents for inhibiting aberrant growth states resulting from hedgehog gain-of-function, ptc loss-of-function or smoothened gain-of-function comprising contacting a cell with a compound, such as a polypeptide or small molecule in an amount sufficient to control the aberrant growth state, e.g., to agonize a normal ptc pathway or antagonize smoothened or hedgehog activity. The present invention further makes available methods and reagents for ameliorating the consequences of hedgehog loss-of-function, ptc gain-of-function, or smoothened loss-of-function comprising contacting a cell with a compound, such as a polypeptide or small molecule, in an amount sufficient to ameliorate the In certain embodiments, the subject compounds, e.g., a cAMP analog, adenylate cyclase agonist, or cAMP phosphodiesterase inhibitor, regulate cAMP levels, which in turn modulates activity of the hedgehog pathway.

Abstract: The present invention relates to rapid, reliable and effective assays for screening and identifying pharmaceutically effective compounds that specifically inhibit the biological activity of fungal GTPase proteins, particularly GTPases involved in cell wall integrity, hyphael formation, and/or other cellular functions critical to pathogenesis. Another aspect of the present invention relates to novel Candida genes and gene products.

Abstract: The present invention relates to rapid, reliable and effective assays for screening and identifying pharmaceutically effective compounds that specifically inhibit the biological activity of fungal GTPase proteins, particularly GTPases involved in cell wall integrity, hyphael formation, and/or other cellular functions critical to pathogenesis. Another aspect of the present invention relates to novel Candida genes and gene products.