Abstract: The invention provides improved chemical synthesizers and methods for their use. In one exemplary embodiment, a chemical synthesizer system has a reaction vessel block having a plurality of reaction vessels which are adapted to hold solid supports. A wash plate is removably attachable to a top end of the reaction vessel block. The wash plate has a plurality of fluid delivery orifices which are aligned with the reaction vessels when the wash plate is attached to the top end of the reaction vessel block. In this way, fluids may be supplied to each of the reaction vessels through the orifices. The system can include a vortex mixer that is held stationary by evacuation a cavity formed between the mixer base and a gasket.

Abstract: A general stochastic method for synthesizing random oligomers on particles is disclosed. A further aspect of the invention relates to the use of identification tags on the particles to facilitate identification of the sequence of the monomers in the oligomer.

Abstract: A general stochastic method for synthesizing random oligomers can be used to synthesize compounds to screen for desired properties. The use of identification tags on the oligomers facilitates identification of oligomers with desired properties.

Abstract: The invention provides systems, devices and methods for synthesizing various chemicals onto solid supports, cleaving the synthesized compounds and preparing samples for analysis. In one exemplary embodiment, the invention provides a device comprising a housing which defines an enclosure. A plate having a plurality of wells is received into the enclosure. Each of the wells has a bottom end and at least some of the wells have a hole in the bottom end. A pressure source is in fluid communication with the holes in the bottom ends of the wells. In this manner, a fluid may be maintained within the wells by application of pressure from the pressure source.

Abstract: The invention provides exemplary systems, methods, and apparatus for distinctly allocating liquids containing chemical compositions or compounds to known locations in an organized manner so that assays may be performed on the compositions, or so that the chemical compositions may be combined with other distinct chemical compositions or reagents prior to evaluation. In an exemplary embodiment, the invention includes a multiwell plate for handling articles such as resin beads suspended in a liquid. The plate comprises a plurality of wells. The wells in turn have a capillary hole that is adapted to (i) retain articles in the well, and (ii) retain liquid in the well while the liquid is not subjected to extrinsic forces, such as centrifugation or vacuum.

Abstract: The invention provides a system and method for synthesizing chemicals onto supports in a parallel manner to produce a combinatorial collection of compounds. The system includes a plurality of middle plates, with each middle plate defining a plurality of reaction zones arranged in a two dimensional array. The reaction zones are adapted to receive a solid support, such as a sheet of membrane, and the middle plates are stackable on each other to form a three dimensional array of reaction zones. The system also includes a pair of end plates, where the middle plates are located between the end plates, and where the end plates include an array of fluid guides corresponding to the array of reaction zones, to allow for selective routing of reagents through the reaction zones.

Abstract: The invention provides systems and methods for processing a plurality of solid supports which preferably have chemical compounds synthesized thereon. According to one exemplary method, the solid supports (12) are held in a common storage location (10). At least some of the solid supports (24) are attracted from the storage location to selected areas within a defined receiving region (20) so that the solid supports which are attracted to the selected areas within the receiving region are separated and spaced apart from each other.

Abstract: A device and method for efficiently synthesizing diverse molecular products on substrates. A parent vessel 200 contains a suspension of substrates. The suspension is pressurized with argon and transferred to a plurality of reaction vessels 201-209 in one or more reaction vessel banks where monomer addition reactions take place. Optionally, the substrates may be tagged with a tag monomer. A vortexing motor 300 vortexes the contents of reaction vessels 201-209 during monomer addition reactions to enhance synthesis. After the desired monomer and/or tag monomer addition reaction, the suspension is pressurized with argon and transferred back to parent vessel 200 for mixing. Thereafter, the suspension may be pressurized with argon and reallocated among reaction vessels 201-209 for further synthesis.

Abstract: Compositions and methods for the solid phase synthesis of organic compounds are provided. The compositions are solid supports having an attached traceless linker precursor and are represented by the formula: ##STR1## In this formula, S.sup.0 is a solid support; B is a connecting group; M is a transition metal, for example ruthenium, chromium, iron, molybdenum and manganese; each L is independently a transition metal ligand; the letter n represents an integer of from 1 to 4, such that M has a sufficient number of ligands to fill the available valences; and X.sup.- represents an anion which is typically a non-nucleophilic anion.

Abstract: The invention provides exemplary systems, methods, and apparatus for distinctly allocating liquids containing chemical compositions or compounds to known locations in an organized manner so that assays may be performed on the compositions, or so that the chemical compositions may be combined with other distinct chemical compositions or reagents prior to evaluation. In one exemplary embodiment, the invention provides a fluid transfer system which comprises a donor member having a plurality of separate regions. At least some of the regions contain at least one chemical composition, with each chemical composition being distinct from any other chemical composition in the donor member. An acceptor member is also provided and includes a plurality of defined locations which are each adapted to receive a liquid medium.

Abstract: The invention provides a method for synthesizing various chemicals onto solid supports, cleaving the synthesized compounds and preparing samples for analysis. In one exemplary embodiment, the invention provides a device comprising a housing which defines an enclosure. A plate having a plurality of wells is received into the enclosure. Each of the wells has a bottom end and at least some of the wells have a hole in the bottom end. A pressure source is in fluid communication with the holes in the bottom ends of the wells. In this manner, a fluid may be maintained within the wells by application of pressure from the pressure source.

Abstract: The invention provides systems, devices and methods for synthesizing various chemicals onto solid supports, cleaving the synthesized compounds and preparing samples for analysis. In one exemplary embodiment, the invention provides a device comprising a housing which defines an enclosure. A plate having a plurality of wells is received into the enclosure. Each of the wells has a bottom end and at least some of the wells have a hole in the bottom end. A pressure source is in fluid communication with the holes in the bottom ends of the wells. In this manner, a fluid may be maintained within the wells by application of pressure from the pressure source.

Abstract: The invention provides exemplary testing devices, systems, and methods for evaluating the permeation of various chemicals through different types of cells. In one exemplary embodiment, a testing device is provided which comprises a base member and a top member having a plurality of wells which are aligned when the top member is secured to the base member. A membrane sheet which includes at least one layer of cells grown on the sheet is placed between the base member and the top member prior to assembly. Test samples are placed into the wells in the top member and samples are removed from the top and bottom wells at a later time and tested to determine the amount of test sample which permeated through the cells.

Abstract: The invention provides systems, methods, and apparatus for dispensing liquids. According to one method, a plate is provided having a plurality of wells. At least one marker is also provided and is associated with at least some of the wells. The plate and marker are moved relative to a plurality of liquid dispensing elements, and the presence of the marker is sensed with a sensor that is disposed at a known location relative to the dispensing elements. The sensing of the marker indicates that at least some of the wells are aligned with the dispensing elements. As such, liquid is dispensed from the dispensing elements and into the aligned wells after sensing the presence of the marker.

Abstract: Novel inhibitors of metalloproteases are disclosed. Such compounds are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, such as rheumatoid arthritis.

Abstract: Peptides of 10 to 40 or more amino acid residues in length and having the sequence X3X4X5GPX6TWX7X8 (SEQ ID NO:252) where each amino acid is indicated by standard one letter abbreviation; X3 is C; X4 is R, H, L, or W; X.sub.5 is M, F, or I; X6 is independently selected from any one of the 20 genetically coded L-amino acids; X7 is D, E, I, L, or V; and X8 is C, which bind and activate the erythropoietin receptor (EPO-R) or otherwise act as an EPO agonist, and methods for their use.

Abstract: The invention provides exemplary testing devices, systems, and methods for evaluating the permeation of various chemicals through different types of cells. In one exemplary embodiment, a testing device is provided which comprises a plate defining at least one well having an open top end. At least one membrane is insertable into the well in a generally vertical orientation to divide the well into separate chambers. The membrane is removable from the well to allow the cells to be grown on the membrane before insertion into the well.

Abstract: The invention provides methods for screening libraries of complexes for compounds having a desired property, especially, the capacity to agonize, bind to, or antagonize a cellular receptor. The complexes in such libraries comprise a compound under test, a tag recording at least one step in synthesis of the compound, and a tether susceptible to modification by a reporter molecule. Modification of the tether is used to signify that a complex contains a compound having a desired property. The tag can be decoded to reveal at least one step in the synthesis of such a compound.

Abstract: Novel inhibitors of metalloproteases, in particular collagenase-1 and stromelysin-1, are disclosed. Such compounds are useful in pharmaceutical compositions and methods for treating or controlling disease states or conditions which involve tissue breakdown, such as rheumatoid arthritis.

Abstract: Described are peptides and peptide mimetics that bind to and activate the thrombopoietin receptor. Such peptides and peptide mimetics are useful in methods for treating hematological disorders and particularly, thrombocytopenia resulting from chemotherapy, radiation therapy, or bone marrow transfusions as well as in diagnostic methods employing labeled peptides and peptide mimetics.