Abstract: The present invention provides a method of biopolymer, esp. oligonucleotide, synthesis. The method consists of coupling a first nucleotide to a second nucleotide in a high surface tension solvent. The invention also provides microdroplets of a soln. comprising a solvent having a b.p. of 150 degree. C. or above, a surface tension of 30 dynes/cm or above, and a viscosity of 0.015 g/(cm)(sec), e.g., propylene carbonate. Such microdroplets are useful for the synthesis of chem. species, particularly biopolymers such as oligonucleotides and peptides, as well as arrays of chem. species. An automated system for oligonucleotide synthesis is described, which comprises delivery of microdroplets by inkjet technol. and computer control of the process. The high surface tension solvent used is selected for compatibility with the inkjet technol.

Abstract: The invention provides a substantially pure Prolactin Releasing Peptide (PrRP) functional analog which suppresses absence seizures in a mammal, and related pharmaceutical compositions. The invention also provides a method of controlling absence seizures in a mammal, by administering to a mammal susceptible to absence seizures an effective amount of PrRP or a PrRP functional analog. Also provided are methods of identifying a compound that modulates AMPA receptor signaling in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to modulate AMPA receptor signaling. The invention also provides methods of identifying a compound for controlling absence seizures in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to control absence seizures in a mammal. Also provided are pharmaceutical compositions for controlling absence seizures in a mammal.

Abstract: The present invention provides a method of diagnosing or predicting susceptibility to an autoimmune disease in an individual by determining the presence or absence in the individual of a 2-2-4 haplotype at the Notch4, HSP70-HOM and D6S273 loci, where the presence of the haplotype diagnoses or predicts susceptibility to the autoimmune disease. The methods of the invention can be particularly useful for diagnosing or predicting susceptibility to Crohn's disease, rheumatoid arthritis or type I diabetes mellitus. In a preferred embodiment, a method of the invention is used to diagnose or predict susceptibility to Crohn's disease in an individual of Ashkenazi Jewish ethnicity.

Abstract: In accordance with the present invention, there are provided novel Schwannomin-Binding-Proteins (SBPs). Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention SBPs can be employed in a variety of ways, for example, for the production of anti-SBP antibodies thereto, in therapeutic compositions and methods employing such proteins and/or antibodies. Also provided are transgenic non-human mammals that express the invention protein.

Abstract: The present invention relates in part to methods for screening for novel enzymatic pathways in environmental samples using metabolic selection strategies, and the isolation of the genes and proteins that make up these pathways.

Abstract: The present invention provides a method of optimizing therapeutic efficacy and reducing toxicity associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. The method of the invention includes the step of determining the level of one or more 6-mercaptopurine metabolites in the patient having an immune-mediated gastrointestinal disorder.

Abstract: Novel synthetic Arg-Gly-Asp containing peptides which have high affinity and specificity for their receptors by virtue of restrictions on their stereochemical conformation. Such restrictions can be provided by cyclization, by inclusion into a constraining conformational structure such as a helix, by providing an additional chemical structure such as an amide or an enantiomer of a naturally occurring amino acid, or by other methods. In particular, there are provided cyclic peptides having increased affinity and selectivity for the certain receptors over that of linear, Arg-Gly-Asp-containing synthetic peptides.

Abstract: The invention provides ligands for melanocortin receptors. For example, the invention provides the melanocortin receptor peptide ligand Ac-Nlc-Gln-His-(p(I)-D-Phe)-Arg-(D-Trp)-Cly-NH2, (SEQ ID NO: 1), where the iodo group is unlabeled or radioactively labeled. The invention additionally provides methods of assaying for melanocortin receptors in a cell or tissue such as brain. The invention also relates to pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a melanocortin receptor ligand and to methods of administering the pharmaceutical composition to a subject. The invention further provides tetrapeptide ligands for melanocortin receptors and methods of altering melanocortin receptor activity.

Abstract: The invention provides a method of reducing the proliferation of a neoplastic cell. The method consists of contacting the neoplastic cell with a cytotoxic or cytostatic binding agent specifically reactive with an aberrantly expressed vesicular membrane associated neoplastic cell specific internalizing antigen. The neoplastic cell specific internalizing anitgen can be selected from the group consisting of lamp-2 and limp II families of lysosomal integral membrane proteins. Also provided is a method of intracellular targeting of a cytotoxic or cytostatic agent to a neoplastic cell population.

Abstract: The present invention provides a method of determining a risk of pouchitis development following a surgical procedure where an internal pouch is created in a patient with ulcerative colitis. The method is practiced by determining in the patient the presence or absence of a pouchitis-associated allele linked to an interferon &ggr; receptor locus, where the presence of the pouchitis-associated allele indicates an increased risk of pouchitis development. The interferon &ggr; receptor locus to which the pouchitis-associated allele is linked can be, for example, an interferon &ggr; receptor 1 gene. A pouchitis-associated allele useful in the invention can be, for example, an allele located within the sixth intron of the interferon &ggr; receptor 1 gene, such as a FA1 microsatellite 171 allele.

Abstract: The present invention relates to an isolated cyclic peptide, theta defensin, having antimicrobial activity, and to theta defensin analogs. A theta defensin can have the amino acid sequence Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa1-Xaa6-Xaa4-Xaa4-Xaa1-Xaa1-Xaa6-Xaa4-Xaa5 -Xaa1-Xaa3-Xaa7-Xaa5, wherein Xaa1 to Xaa8 are defined; wherein Xaa1 can be linked through a peptide bond to Xaa8; and wherein crosslinks can be formed between Xaa3 and Xaa3, between Xaa5 and Xaa5, and between Xaa7 and Xaa7. For example, the invention provides a theta defensin having the amino acid sequence Gly-Phe-Cys-Arg-Cys-Leu-Cys-Arg-Arg-Gly-Val-Cys-Arg-Cys-Ile-Cys-Thr-Arg (SEQ ID NO:1), wherein the Gly at position 1 (Gly-1) is linked through a peptide bond to Arg-18, and wherein disulfide bonds are present between Cys-3 and Cys-16, between Cys-5 and Cys-14, and between Cys-7 and Cys-12. The invention also relates to antibodies that specifically bind a theta defensin and to isolated nucleic acid molecules encoding a theta defensin.

Abstract: Isolated nucleic acids encoding a novel MAR-binding protein are also provided, as well as vectors containing the nucleic acids and recombinant host cells transformed with such vectors. The invention further provides methods of detecting such nucleic acids by contacting a sample with a nucleic acid probe having a nucleotide sequence capable of hybridizing with the isolated nucleic acids of the present invention. Such probes can correspond to the ATC sequences.

Abstract: Methods for rapidly identifying drug candidates that bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

Abstract: A high throughput device is provided for simultaneously isolating periplasmic fractions from multiple samples of host cells. The device can be formatted to operate in a series. A method for simultaneously isolating multiple periplasmic fractions is also provided. The method includes (a) providing a high throughput device for isolating periplasmic fractions from multiple samples of host cells having an outer membrane via attaching a removable sample chamber having a membrane chamber wall to a vacuum chamber and applying a vacuum thereto (b) removing media with the vacuum and (c) removing the outer membrane of the host cells (d) attaching a collection chamber to the vacuum chamber and applying a vacuum thereto in order to carry out a collection of the periplasmic fractions that pass through the membrane of the chamber wall from the host cells.

Abstract: This invention is directed toward mutated DNA, proteins, or protein fragments and particles from the L-2 cell line. The invention is also directed to diagnostic, prophylactic and therapeutic methods of making and using the DNA, proteins and particles.

Abstract: Sulfotransferases that synthesize the HNK-1 carbohydrate epitope by adding a sulfate group to GlcA&bgr;1→3Gal&bgr;1→4GlcNAc&bgr;1→R to form glycan sulfo→3GlcA&bgr;1→3Gal&bgr;1→4GlcNAc&bgr;1→R. They are exemplified by human (hu-HNK-1ST) and mouse (mHNK-1ST) sulfotransferases. Also provided are related peptides, antibodies, nucleic acids and methods.

Abstract: The present invention provides nucleic acid and amino acid sequence of the novel I-1 and I-2 polypeptides, which are associated with human inflammatory bowel disease (IBD). Methods of diagnosing and treating inflammatory bowel disease using the IBD-associated I-1 and I-2 antigens also are provided.

Abstract: This invention is directed to a novel &bgr;-secretase that produces the A&bgr; peptide found in Alzheimer's Disease. One &bgr;-secretase is a protein having a molecular weight of about 61, 81 or 88 kDa that cleaves an amyloid precursor protein (APP) substrate. Another is a protease complex having a molecular between about 180 and 200 kDa, which, in one embodiment, contains the 61, 81, and 88 kDa proteins and, in another embodiment, contains proteins having a molecular weight of about 66, 60, 33 and 29 kDa. Another &bgr;-secretase has a molecular weight between about 50 and 90 kDA. The invention is also directed to methods of selecting agents that inhibit A&bgr; peptide production and treating Alzheimer's disease in patients.

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.