Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with a D-configuration hydroxyproline ether or thioether converts bradykinin agonists into bradykinin antagonists. The invention further includes the intermediate compounds and additional modifications at other positions within the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.

Abstract: Novel backbone-cyclized BPI peptide analogs and methods of making the same by the use of bridging groups attached via the alpha nitrogens of amino acid derivatives to provide novel non-peptidic linkages. Novel building units used in the synthesis of these backbone-cyclized peptide analogs are N&agr;-functionalized amino acids constructed to include a spacer and a terminal functional group. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. A plurality of these N&agr;&ohgr;-functionalized amino acids are incorporated into a library of peptide sequences, preferably during solid phase peptide synthesis.

Abstract: The present invention relates to methods for the identification of nucleic acid sequences encoding members of a multimeric (poly)peptide complex by screening for polyphage particles. Furthermore, the invention relates to products and uses thereof for the identification of nucleic acid sequences in accordance with the present invention.

Abstract: An apparatus and method for screening combinatorial libraries of materials by measuring the response of individual library members to mechanical perturbations is described. The apparatus generally includes a sample holder for containing the library members, an array of probes for mechanically perturbing individual library members, and an array of sensors for measuring the response of each of the library members to the mechanical perturbations. Library members undergoing screening make up a sample array, and individual library members constitute elements of the sample array that are confined to specific locations on the sample holder. During screening, the apparatus mechanically perturbs individual library members by displacing the sample array (sample holder) and the array of probes. Typically, all of the elements of the sample array are perturbed simultaneously, but the apparatus also can also perturb individual or groups of sample array elements sequentially.

Abstract: A method for in vitro selection, from a library of catalyst molecules, of a catalyst molecule of interest having a relatively more efficient specific catalytic activity of interest, as compared to the rest of the catalyst molecules within said library, and wherein said in vitro selection method is characterised by that it allows multiple catalytic activity turn-overs (i.e. substrate to product catalytic activity turn-overs), by the catalyst molecule of interest, before it is finally collected.

Abstract: The present invention relates to a method for obtaining nucleic acid sequences encoding (poly)peptides which increase the expression yields of periplasmic proteins in functional form upon co-expression of said (poly)peptides and said periplasmic proteins. The invention also provides a method for the identification of said (poly)peptides. Furthermore, the present invention relates to a method for increasing the expression yields of periplasmic proteins in functional form by co-expressing (poly)peptides, for example Skp, FkpA, or a homolog of Skp or FkpA, in bacteria.

Abstract: The invention provides a method of contrast agent drug candidate selection which involves: (i) obtaining a combinatorial library comprising an admixture of potential contrast agent drug candidates each incorporating a reporter moiety which is detectable in the animate human or non-human animal body (e.g. mammalian, avian or reptilian body), said library comprising a plurality of said reporter moieties which are interdistinguishably detectable in said body; (ii) administering said library to an animate human or non-human animal body; (iii) identifying in vivo one or more of said reporter moieties which has a desired distribution and/or elimination pattern in said body and thereby identifying a member of said library which has said pattern site or a sub-set of said library which contains a member of said library which has said pattern.

Abstract: The present invention relates generally to a method of identifying modulators of biological interactions and agents useful for same. More particularly, the present invention contemplates a method of detecting inhibitors of biological interactions involving proteinaceous and/or nucleic acid molecules and more particularly a method of identifying peptide inhibitors of biological interactions having adverse effects on living cells, tissue or organisms. The present invention provides the means by which a wide range of peptide-based therapeutic, prophylactic and diagnostic reagents may be developed.

Abstract: A novel encoding system, compositions for use therein and methods for determining the source, location and/or identity of a particular item or component of interest is provided. In particular, the present invention utilizes a collection of one or more sizes of populations of semiconductor nanocrystals having characteristic spectral emissions, to “track” the source or location of an item of interest or to identify a particular item of interest. The semiconductor nanocrystals used in the inventive compositions can be selected to emit a desired wavelength to produce a characteristic spectral emission in narrow spectral widths, and with a symmetric, nearly Gaussian line shape, by changing the composition and size of the semiconductor nanocrystal. Additionally, the intensity of the emission at a particular characteristic wavelength can also be varied, thus enabling the use of binary or higher order encoding schemes.

Abstract: A method of fabricating an array with multiple sets of neighboring features. In the method, for each of multiple sets of neighboring features, at least one set of drops is deposited from a corresponding same pulse jet dispenser onto a substrate so as to form the array with the sets formed from drops deposited by respective different dispensers. Apparatus and computer program products which can execute a method of the invention, are also provided.

Abstract: The present invention provides a method of cloning a protein coding for a membrane protein without the need of using anyantibody or ligand. The method of cloning a membrane protein comprises selecting a protein having a signal sequence, using a DNA coding for the signal sequence and N-terminal sequence of the protein as the reporter gene, and screening for a gene for a protein having a transmembrane domain(s). The present invention is concerned also with the CDNA obtained by using such method, a vector containing the DNA, a transformant as transformed with the vector, and the transcription product of the DNA as produced by the transformant.

Abstract: The present disclosure identifies substances having the property of binding to cyclin dependent kinase (cdk) comprising: (i) a peptide including amino acid residue 84 to 103 of full length p16 protein, or an active portion or derivative thereof; or (ii) a functional mimetic of the fragment, active portion or derivative; the substance excludes full length p16, p15, p18 and p19 proteins. These substances are useful in tumor suppression by inhibiting the phosphorylation of Rb protein. Also described herein is the resolution of the amino acid motifs responsible for binding cdks, an FLD motif, corresponding to amino acid residues 90 to 92 of full length p16 protein, and an LVVL motif, corresponding to amino acid residues 94 to 97 of full length p16 protein. The substances disclosed herein can be used in the treatment of hyperproliferative disorders and to screen and design molecules having the similar properties.

Abstract: Compositions, kits, and methods are provided for use in a recombinational cloning or subcloning methods for constructing expression vectors which comprise: ligating a library of double-stranded linear donor DNAs, where each member of the library includes a donor DNA sequence, with a double-stranded linear driver DNA which includes a promoter sequence and a donor recombination site to form a single circular donor DNA, the single circular donor DNA not including an origin of replication, where the donor DNA sequence is under the transcriptional control of the promoter; and contacting the circular donor DNA and a circular acceptor acceptor vector in the presence of a recombinase to form a single fused circular vector, the circular acceptor vector comprising an origin of replication and an acceptor recombination site capable of recombining with the circular donor DNA.

Abstract: An apparatus and method for synthesizing a combinatorial library comprising a plurality of chemical compounds such that the chemical composition of each compound is easily tracked. The library compounds are synthesized on solid-phase supports, which are spatially arranged in frames during synthesis according to a predetermined protocol, such that each solid-phase support passes through a series of unique spatial 2D or 3D addresses by which the chemical composition of each compound may be determined at any point during synthesis. Solid-phase supports include hollow tubular-shaped lanterns and gears.

Abstract: The present invention relates to the field of compounds which are substrates or inhibitors of proteolytic enzymes and to apparatus and methods for identifying substrates or inhibitors for proteolytic enzymes. We have devised a combinatorial method for the rapid indentification of binding motifs which will greatly expedite the synthesis of inhibitors of a variety of proteolytic enzymes such as aspartyl proteases, serine proteases, metallo proteases and cysteinyl proteases.

Abstract: Electrochemiluminescent-labels and enzyme substrates, which preferably are conjugated, are used in immunoassays and electrochemiluminescence is generated catalytically. In conventional electrochemiluminescence immunoassays, an anti-analyte antibody molecule can give rise to typically 6-8 electrochemiluminescence-active ruthenium atoms, while in the present invention, each enzyme-labeled anti-analyte molecule can give rise to thousands of electrochemiluminescence-active ruthenium atoms per second. An exemplary immunoassay is based on a catalytic process employing &bgr;-lactamase-conjugated anti-analytes which enzymatically hydrolyze electrochemiluminescent-labeled substrates, making them strongly electrochemiluminescent. The electrochemiluminescence signal generated by each anti-analyte molecule (i.e., each analyte molecule) is much greater than with the conventional method. Accordingly, greater sensitivity can be gained in the measurement of low concentrations of a given immunoassay analyte.

Abstract: The disclosed synthesis system is based on the idea of designing a synthesis and treatment procedure, substrates and anchor groups which enable biomolecules to be simultaneously produced in an entirely automatic manner. By using a pipetting robot to dispense the reagents, the reaction column can be arranged in a format suitable for subsequent treatment. For a pipetting robot to carry out even water-sensitive or air-sensitive synthesis protocols, certain structural measures must be taken. The operation principle of the automated and the synthesis sequence are described below as an example of a possible solution. The automation can work with conventional substrates and reagents. Handling, however, is simplified by new, specially adapted substrates and anchor groups. A special, simultaneous purification and aliquot portioning process improves product quality and makes the device easier to use.

Abstract: The invention provides a tri- or tetra-valent monospecific antigen-binding protein comprising three or four Fab fragments bound to each other covalently by a connecting structure, which protein is not a natural immunoglobuline. Further provided are novel connecting structures for use in assembling the proteins of the invention and means for attaching a labeling or effector group thereto. The proteins of the invention are useful, for example, in the treatment and diagnosis of cancer.

Abstract: Islet cell membrane antigen has been purified and, since it displaces islet cell surface antibodies, is of utility in the prevention or treatment of diabetes.

Abstract: A method is disclosed for obtaining affinity ligands for isolating tissue-type plasminogen activator (tPA). Ligands binding tPA with high specificity at pH 7 and releasing tPA at pH 5 or lower are disclosed. Also disclosed are methods whereby additional ligands having desirable preselected binding and release (elution) characteristics may be isolated, permitting the development of tailored ligands to meet the purification problems presented by any particular feed stream containing tPA.