Abstract: The present invention provides of using multimeric MHC class II/peptide complexes. In one aspect, methods provided for identifying MHC class II-restricted immune epitopes of a predetermined polypeptide antigen. Methods for identifying an immunostimulatory epitope for a predetermined polypeptide antigen are provided. In a related aspect, methods for screening a therapeutic polypeptide agent for an MHC class II epitope are provided. In other aspects, methods for modulating T cells and for determining or monitoring an MHC class II-restricted immune status of a patient are also provided.

Abstract: Described herein are methods for identifying and preparing bivalent binding molecules to 7 transmembrane G protein-coupled receptors. The methods disclosed herein are based on the SELEX method for generating high affinity nucleic acid ligands. SELEX is an acronym for Systematic Evolution of Ligands by EXponential enrichment. The methods of this invention combine two or more binding domains to two or more different epitopes of the same 7 transmembrane G protein-coupled receptor. These bivalent binding molecules are useful as therapeutic and diagnostic agents.

Abstract: It is intended to provide a method of reusing a DNA-immobilization substrate whereby the expensive DNA-immobilization substrate can be efficiently utilized and a reusable DNA-immobilization substrate having the same performance as a new product without any trouble in practical use can be provided. Namely, a method of reusing a DNA-immobilization substrate characterized in that, to remove DNA from a DNA-immobilization substrate carrying the DNA immobilized by an acid-amide bond via an oligonucleotide to thereby enable the immobilization of a fresh DNA, the acid-amide bond between the substrate and the DNA is hydrolyzed with an acid or an alkali.

Abstract: The invention relates to a modified phage display method for detecting and identifying target and target binders. The modified methods involve transforming host cells with two separate phages of a target or target library and a target-binder library, and selecting to eliminate the non-paired targets and binders. The invention also relates to antibodies that bind to complexes of target and target binders; nucleic acids encoding target and target binders peptides; and the use of sequence information inherent in the targets and target binders for target validation using in silico approaches. The invention further relates to diagnostics and therapeutics employing the disclosed target and target binder peptides or polynucletides and their use in small molecule drug discovery; diagnostic and therapeutic applications directed to cancers and similar disorders; and site directed assays for high throughput drug screening.

Abstract: Novel metal binding ligands are disclosed that may be coupled to peptides for use in methods of diagnosis and therapy. Peptides containing the ligands are produced using a method wherein ligand introduction or cyclization can be conducted at any point during the synthesis of the peptide. Such peptide derivatives are readily labeled with radiometals, such as isotopes of rhenium or technetium, while retaining their ability to tightly bind specific peptide receptors.

Abstract: Peptides which are mimotopes of the hypervariable region 1 (HVR1) of the putative envelope protein E2 of hepatitis C virus (HCV) are provided, useful in obtaining antibodies and raising an immune response cross-reactive against different strains of HCV.

Abstract: The present invention provides methods and devices for making new and inexpensive miniarrays suitable for gene expression analysis. Also provided herein are methods of diagnosis for specific tissue or condition using specialized diagnostic miniarrays that exhibit specific visual pattern as diagnostic readout.

Abstract: A method for discovering one or more peptides adapted for specific binding to a microorganism of interest. The method comprises (i) identifying an antimicrobial peptide having antimicrobial activity against the microorganism of interest, (ii) generating a library of first generation mutants of the antimicrobial peptide, each of the first generation mutants differing from the antimicrobial peptide by a small number of amino acid substitutions, additions or deletions, (iii) screening the library of first generation mutants for those first generation mutants that bind to the microorganism of interest, (iv) determining the peptide sequences of those first generation mutants that bind to the microorganism of interest, and (v) if necessary, repeating steps (ii) through (iv) for one or more successive generations of mutants until one or more consensus peptide sequences emerge.

Abstract: Method and apparatus for constructing a cDNA library by hybridizing mRNA with oligo (dT) on a support and treating with a reverse transcriptase to immobilized complementary DNA, or for constructing a gDNA library by ligating a double-stranded chromosomal DNA library with an oligonucleotide on a support having a restriction enzyme site and then immobilizing the gDNA library.

Abstract: The present invention provides a method for identifying a modulator or mediator of a biological activity, which activity includes antigenicity and or immunogenicity, said method comprising the step of: (i) producing a gene fragment expression library derived from defined nucleotide sequence fragments; and (ii) assaying the expression library for at least an amino acid sequence derived from step (i) for a biological activity wherein that activity is different from any activity the amino acid sequence may have in its native environment.

Abstract: The invention provides a method for producing a zinc finger polypeptide which binds to a target nucleic acid sequence containing a modified base but not to an identical sequence containing an equivalent unmodified base.

Abstract: A process for screening an expression library to identify clones expressing enzymes having a desired activity is provided. The process involves first generating from genomic DNA samples of one or more microorganisms an expression library comprising a plurality of recombinant cell clones, and then introducing into capillaries in a capillary array a substrate and at least a subset of the clones, either individually or as a mixture. Interaction of the substrate and a clone expressing an enzyme having the desired activity produces an optically detectable signal, which can then be spatially detected to identify capillaries containing clones producing such a signal. The signal-producing clones can then be recovered from the identified capillaries.

Abstract: The invention relates to the formation of novel in vivo combinatorial enzyme complexes for use in screening candidate drug agents for bioactivity.

Abstract: The present invention relates to novel assays for assessing the degree to which a cell is metabolically active. Also provided, are mutagenicity assays and, more specifically, methods for determining whether a given agent is genotoxic. Embodiments of the assays employ a microorganism, or a mammalian cell, that has been genetically modified to produce light when the presence of test agent results in a mutation, e.g., reversion or forward, in the DNA of such microorganism or cell.

Abstract: The present invention provides peptides with a specific affinity for glycosaminoglycan molecules. These peptides may have any number of functions, including but not limited to use as inhibitors of glycosaminoglycan-mediated processes, enhancers of glycosaminoglycan-mediated processes, and as molecular probes to identify the presence of a specific glycosaminoglycan. Peptides of the invention may be directed against any glycosaminoglycan, including hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, heparin, keratan sulfate, keratosulfate, chitin, chitosan 1, and chitosan 2. These isolated peptides may have therapeutic uses in the treatment or prevention of diseases involving infection, inflammatory diseases, cancer, infections, etc. The peptides may also have other biological functions such as contraception.

Abstract: Methods, arrays and kits are provided for rapidly and efficiently identifying and quantifying multiple different activated transcription factors in a biological sample at the same time. In one aspect, a method is provided for isolating DNA probes which bind to activated transcription factors, including the step of mixing a library of double stranded DNA probes with a sample containing activated transcription factors. The transcription factor probes that have bound to the activated transcription factors are isolated from the mixture via an agarose gel separation. The bound probes can be identified, for example, by using an array of hybridization probes.

Abstract: The invention is directed to a model system for structure-activity relationship analysis of peptide or protein molecules involved in important biological processes. Provided by the invention are combinatorial peptide libraries comprising peptides with a novel “tryptophan zipper” scaffold (trpzip) that forms stable ?-hairpin structure in solution. Methods of selecting and using such scaffold are provided herein, which are useful for mimicking native protein structures and interactions and designing therapeutic agents. Thus, the invention has profound utility for biological studies and drug development.

Abstract: Identification of the molecular targets of a drug or toxin is the first step in understanding how the drug or toxin works, an important advance in learning how to improve a drug or assess the risks due to a toxin. The primary action of a drug usually involves binding to a protein; secondary actions may express themselves in the form of side effects and in some cases may be due to binding to other proteins. Consequently, it is useful to identify all physiologically relevant sites of action of a drug or toxin. A simple method for obtaining a list of the potential targets of a drug, toxin or other biologically active substance (referred to collectively as ligands) involves a multistep process. The first step is screening a protein or peptide library to identify library members that exhibit high affinity for a particular ligand. The second step involves searching of sequence data bases for proteins that contain the sequences of the library members shown to have high affinity for the ligand.

Abstract: The present invention provides peptide derivatives with a specific affinity for glycosaminoglycan molecules. These peptide derivatives include multimers as well as chemically modified peptides and may be prepared by a variety of methods. The peptides of the invention have numerous functions, including but not limited to use as inhibitors of glycosaminoglycan-mediated signaling events and targeting agents. Peptides of the invention may be directed against any glycosaminoglycan, including hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, heparin, keratan sulfate, keratosulfate, chitin, chitosan 1, and chitosan 2. The peptide derivatives of the invention also have therapeutic uses in the treatment and prevention of diseases involving inflammatory diseases, cancer, and cancer metastasis, autoimmune diseases, etc.

Abstract: The invention provides a process for preparing capped mRNAs from an RNA mixture, e.g. whole RNA isolated from a cell or tissue extract, that includes combining in a reaction mixture RNA comprising capped mRNA with a separable affinity matrix having high-affinity eIF4E bound thereto, under conditions sufficient for binding to occur between the high-affinity eIF4E and the capped mRNA, whereby capped mRNA is bound to the affinity matrix, separating the affinity matrix from the reaction mixture, then separating the capped mRNA from the affinity matrix. High affinity eIF4E mutants previously described are employed in the process as well as a novel mutant disclosed and claimed herein. The mRNA preparation process is based on isolation of 5?-capped mRNA. The mRNA molecules thus isolated have intact sequences encoding the NH2-terminal ends of the proteins they encode, unlike those isolated by prior methods.