Abstract: The present invention provides methods for in vivo panning of a library to identify molecules that specifically home to a selected organ.

Abstract: The present invention provides a heart homing peptide that contains the amino acid sequence GGGVFWQ (SEQ ID NO: 2); HGRVRPH (SEQ ID NO: 3); VVLVTSS (SEQ ID NO: 4); CLHRGNSC (SEQ ID NO: 9); or CRSWNKADNRSC (SEQ ID NO: 10) and further provides conjugates in which a heart homing peptide is linked to a moiety such as a therapeutic agent. The conjugates of the invention are useful for treating cardiovascular diseases such as atherosclerosis and restenosis.

Abstract: The present invention relates to analogs of indolicidin, which is a naturally occurring peptide having the amino acid sequence Ile-Leu-Pro-Trp-Lys-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-NH2 (“Indol 1-13;” SEQ ID NO: 1). The indolicidin analogs of the invention include, for example, analogs such as Indol 2-13 (SEQ ID NO: 2) and Indol 3-13 (SEQ ID NO: 3), which are truncated at the amino terminus by one and two amino acids, respectively, as compared to Indol 1-13 (SEQ ID NO: 1); analogs in which at least one Trp residue in an amino terminal truncated indolicidin analog is replaced by a Phe residue (“Indol/F”) analogs”); indolicidin analogs comprising, at the carboxy terminus, a homoserine residue; and fusion polypeptides comprising an indolicidin analog. In addition, the invention provides nucleic acid molecules encoding the indolicidin analogs of the invention or precursors of such analogs.

Abstract: The present invention provides substantially purified cryptdin peptides having a consensus amino acid sequence: X1-C-X2-C-R-X3-C-X4-E-X5-C-X6-C-C-X7 wherein X1 is 3 to 9 amino acids; X2 is one amino acid, preferably Y, H or R; X3 is 2 or 3 amino acids; X4 is three amino acids; X5 is five amino acids; X6 is 6 to 10 amino acids; and X7 is 0 to 9 amino acids.

Abstract: The present invention provides enriched library fractions containing a plurality of molecules that home to a selected organ in vivo.

Abstract: Methods for treating erectile dysfunction in males and sexual dysfunction, such as sexual arousal disorder, in females. The methods involve administering an effective dose of certain compounds, such as HP-228, having the generic formula X1-X′2-(D)Phe-Arg-(D)Trp-X3.

Abstract: The present invention provides a method of inhibiting an activity of a cell regulatory factor comprising contacting the cell regulatory factor with a purified polypeptide, wherein the polypeptide comprises the cell regulatory factor binding domain of a protein and wherein the protein is characterized by a leucine-rich repeat of about 24 amino acids. In a specific embodiment, the present invention relates to the ability of decorin, a 40,000 dalton protein that usually carries a glycosaminoglycan chain, to bind TGF-&bgr;. The invention also provides a novel cell regulatory factor designated MRF. Also provided are methods of identifying, detecting and purifying cell regulatory factors and proteins which bind and affect the activity of cell regulatory factors. The present invention further relates to methods for the prevention or reduction of scarring by administering decorin or a functional equivalent of decorin to a wound.

Abstract: Methods for screening cDNAs that express a product interacting with a target molecule. Individual cDNAs are pooled and the cDNA pools are expressed to obtain expression products, for example by coupled in vitro transcription/translation. The interaction of the products with the target molecule is then assayed, for example by scintillation proximity assay (SPA), to identify pools of interest. By selectively re-pooling the cDNAs and repeating the expression and assay steps, individual cDNAs of interest can be rapidly identified. This method is readily automated in a computer-controlled device for high throughput screening. The invention also provides methods of transfecting a cell with a cDNA identified by the screening method to confer a desired property to a cell or identifying cDNAs from a pool of cDNAs by transfection into cells to confer a desired property.

Abstract: The invention relates to the discovery and purification of novel intracellular vitamin D binding proteins (IDBPs) and the isolation of polynucleotide sequences encoding the proteins. IDBPs are of interest because they mediate the vitamin D resistance, i.e., insensitivity, observed in new world primates. IDBPs are distinct from the vitamin D receptor and other intracellular receptors, e.g. estrogen receptor. One aspect of the invention is to provide purified IDBPs as pharmaceutical compositions to affect steroid hormone activity. Another aspect of the invention provides polynucleotides encoding the IDBPs of the invention for use in altering the expression of IDBPs. Yet another aspect of the invention is to provide assays for the detection or screening of therapeutic compounds that interfere with the interaction between IDBP and vitamin D (or other ligands that bind to IDBP), and the use of such compounds as pharmaceutical compositions.

Abstract: The present invention provides a mammalian CD40-associated protein (CAP), a nucleic acid molecule encoding the CAP and antibodies specific for the CAP. The invention further provides a substantially purified human CAP-1 and a nucleic acid molecule encoding human CAP-1. The invention also provides screening assays for identifying an agent that effectively alters the association of a CAP with a second molecule, which can bind to the CAP. In addition, the invention provides methods for identify a CAP agonist or CAP antagonist that can increase or decrease, respectively, the level of expression of the CAP in a cell. Such an effective agent, agonist or antagonist can modulate a function of a cell such as a humoral immune response or cell growth. The invention also provides methods of detecting a CAP in a sample by detecting the CAP or a nucleic acid molecule encoding the CAP. Such methods can be used to diagnose a pathology that is characterized by an increased or decreased level of a CAP in a cell.

Abstract: A composition of matter comprising a plurality of procaryotic cells containing a diverse population of expressible oligonucleotides operationally linked to expression elements, said expressible oligonucleotides having a desirable bias of random codon sequences.

Abstract: This invention provides a method of determining the proteolytic activity of the in vivo secretases, particularly the &bgr;-secretase and &ggr;-secretase that produce the A&bgr; peptides found in the plaques of Alzheimer Dementia (AD) patients. The invention also provides methods of isolating such secretases and methods of selecting agents that affect the activity of such secretases for developing drugs to treat or prevent dementia.

Abstract: The present invention provides novel cytokine restraining agents, which limit or control the biological activity of cytokines. The invention also provides pharmaceutical compositions comprising a cytokine restraining peptide and methods of administering the pharmaceutical composition to a subject. The invention further provides methods for using the novel peptides to restrain cytokine activity in a subject.

Abstract: Method for the isolation and characterization of a 140,000 dalton cell surface glycoprotein with the properties expected of a fibronectin receptor is described.

Abstract: The present invention provides substantially pure proapoptotic dependence peptides. The peptides consist substantially of the sequence of an active dependence domain selected from the group of dependence polypeptides consisting of p75NTR, androgen receptor, DCC, huntingtin polypeptide, Machado-Joseph disease gene product, SCA1, SCA2, SCA6 and atrophin-1 polypeptide. Substantially pure proapoptotic dependence peptides include SATLDALLAALRRI (SEQ ID NO:3), Q14 (SEQ ID NO:7), SATLDALLAALGGI (SEQ ID NO:4), SATLDALLAALRGI (SEQ ID NO:5), SATLQALLAALRRI (SEQ ID NO:6), tat-GG-SATLDALLAALRRI (SEQ ID NO:37) and tat-GG-Q14 (SEQ ID NO:36).

Abstract: The present invention provides molecules that selectively home to various normal organs or tissues, including to lung, pancreas, skin, retina, prostate, ovary, lymph node, adrenal gland, liver or gut; and provides molecules that selectively home to tumor bearing organs or tissues, including to pancreas bearing a pancreatic tumor or to lung bearing a lung tumor. The invention also provides conjugates, comprising an organ or tissue homing molecule linked to a moiety. Such a moiety can be, for example, a therapeutic agent or a detectable agent. In addition, the invention provides methods of using an organ homing molecule of the invention to identify a particular organ or tissue by contacting the organ or tissue with a molecule of the invention.

Abstract: The present invention relates to an action between an inhibitor of apoptosis (IAP) protein and members of the caspase family of cell death proteases, for example, an interaction of the X chromosome linked IAP (XIAP) and caspase-3, caspase-7 or caspase-9, wherein the IAP regulates the activity of the caspases. The invention provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a caspase such as caspase-3 or caspase-7. The invention also provides screening assays for identifying agents that alter the specific association of an IAP such as XIAP, c-IAP-1 or c-IAP-2 and a pro-caspase such as pro-caspase-9. In addition, the invention also provides methods for identifying agents that modulate the activity of a caspase in the presence of an IAP and that regulate the activation of a pro-caspase by an IAP.

Abstract: The present invention provides vaccines and a means of vaccinating a vertebrate so as to prevent or control specific T cell mediated pathologies, including autoimmune diseases and the unregulated replication of T cells. The vaccine is composed of a T cell receptor (TCR) or a fragment thereof corresponding to a TCR present on the surface of T cells mediating the pathology. The vaccine fragment can be a peptide corresponding to sequences of TCRs characteristic of the T cells mediating said pathology. Such a peptide can bind to conventional antigens completed to MHC antigen presenting cells or to superantigens. Means of determining appropriate amino acid sequences for such vaccines are also provided. The vaccine is administered to the vertebrate in a manner that induces an immune response directed against the TCR of T cells mediating the pathology. This immune response down regulates or deletes the pathogenic T cells, thus ablating the disease pathogenesis.

Abstract: The present invention provides a highly sensitive method of diagnosing inflammatory bowel disease (IBD) in an individual. The method includes the steps of isolating a sample from the individual; determining by non-histological means whether the sample is positive for anti-neutrophil cytoplasmic antibodies (ANCA); determining whether the sample is positive for anti-Saccharomyces cerevisiae immunoglobulin A (ASCA-IgA); determining whether the sample is positive for anti-Saccharomyces cerevisiae immunoglobulin G (ASCA-IgG); and diagnosing the individual as having IBD when the sample is positive for ANCA, ASCA-IgA or ASCA-IgG, and diagnosing the individual as not having IBD when the sample is negative for ANCA, ASCA-IgA and ASCA-IgG, provided that the method does not include histological analysis of neutrophils.

Abstract: The present invention provides a new family of cysteine-rich antimicrobial peptides isolated from bovine neutrophils herein named beta defensins. Thirteen structurally homologous peptides were purified to homogeneity from a granule-rich cytoplasmic fraction of purified blood neutrophils. These antimicrobial compounds are useful in human and veterinary medicine, and as agents in agricultural, food science, and industrial applications.