Abstract: An apparatus for high-throughput combinatorial synthesis of organic molecules including a reaction vessel for containing a combinatorial chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis or rotation. A method of combinatorial synthesis of organic molecules is also disclosed.

Abstract: An apparatus for high-throughput combinatorial syntheses of organic molecules including a reaction vessel for containing a combinatorial-chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis of rotation. A method of combinatorial synthesis of organic molecules is also disclosed.

Abstract: Described is a system and method for synthesizing polymeric molecules such as oligonucleotides and polypeptides. The system is capable of continuously synthesizing molecules by providing an array of reaction sites and an array of stations for carrying out synthetic manipulations. The reaction sites in the former array can be placed in a fixed order and at fixed intervals relative to each other. Similarly, the stations can be placed in a fixed order and at fixed intervals relative to each other. The two arrays can be moved relative to each other such that the stations carry out desired steps of a reaction scheme at each reaction site. The relative locations of the stations and the schedule for the relative movement can correlate with the order and duration of reaction steps in the reaction scheme such that once a reaction site has completed a cycle of interacting with the full array of stations then the reaction scheme is complete.

Abstract: Described is a system and method for synthesizing polymeric molecules such as oligonucleotides and polypeptides. The system is capable of continuously synthesizing molecules by providing an array of reaction sites and an array of stations for carrying out synthetic manipulations. The reaction sites in the former array can be placed in a fixed order and at fixed intervals relative to each other. Similarly, the stations can be placed in a fixed order and at fixed intervals relative to each other. The two arrays can be moved relative to each other such that the stations carry out desired steps of a reaction scheme at each reaction site. The relative locations of the stations and the schedule for the relative movement can correlate with the order and duration of reaction steps in the reaction scheme such that once a reaction site has completed a cycle of interacting with the full array of stations then the reaction scheme is complete.

Abstract: A method of forming a solid-phase support, the method including the steps of providing a substrate having a reaction vessel, dispensing a particle in the reaction vessel, and permanently bonding the particle in the substrate within the reaction vessel. The particle may include a microbead. The particle may include controlled pore glass. A method of synthesis is also disclosed that includes including the steps of providing a solid-phase support including a particle embedded to the substrate adjacent a surface of substrate, the particle being functionalized to covalently attach an intermediate compound of a synthetic reaction, dispensing a liquid including a reagent to the solid-phase support to effect the synthetic reaction, and removing the liquid from the solid-phase support by centrifugation, whereby the intermediate compound remains attached to the substrate by the particle.

Abstract: A simple, efficient apparatus and method for separating layers of immiscible or partially miscible liquids useful in methods of high-throughput combinatorial organic synthesis or parallel extraction of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis or purification (extraction). In a preferred embodiment, an apparatus and method for separating layers of immiscible or partially miscible liquids compatible with microtiter plate type array(s) of reaction vessels is disclosed. Another application of centrifugation based liquid removal was found for washing the plates in biological assays or synthesis on modified substrates.

Abstract: An apparatus for parallel monitoring of a plurality of chemical reactions, each chemical reaction occurring within a respective one of a plurality of wells. The apparatus includes a lighting device for illuminating the plurality of wells, the lighting device having an light emitting diode (LED) array, a camera device configured to obtain images of the plurality of wells and saving the images to an image storage location, the camera device having a charge couple device (CCD) capable of imaging the plurality of wells simultaneously, a viewing program for viewing one or more of the saved images, and an analyzing program for opening each saved image and geometrically registering each saved image in order to determine a specific value corresponding to each one of the chemical reactions at the time the image was obtained, the analyzing program saving the specific values to an analysis results storage location. A method of utilizing the apparatus is also disclosed.

Abstract: A simple, efficient apparatus and method for separating layers of immiscible or partially miscible liquids useful in methods of high-throughput combinatorial organic synthesis or parallel extraction of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis or purification (extraction). In a preferred embodiment, an apparatus and method for separating layers of immiscible or partially miscible liquids compatible with microtiter plate type array(s) of reaction vessels is disclosed. Another application of centrifugation based liquid removal was found for washing the plates in biological assays or synthesis on modified substrates.

Abstract: The invention provides compounds which specifically inhibit factor Xa activity having the structure A1—A2—(A3)m—B, where m is 0 or 1. A compound of the invention is characterized, in part, in that it exhibits a specific inhibition of factor Xa activity with a Ki≦100 &mgr;M, preferably ≦2 nM, and does not substantially inhibit the activity of other proteases involved in the coagulation cascade. The invention further provides methods of specifically inhibiting the activity of factor Xa and of inhibiting blood clotting in vitro and in an individual and methods of detecting factor Xa levels or activity.

Abstract: An apparatus for high-throughput combinatorial syntheses of organic molecules including a reaction vessel for containing a combinatorial-chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis of rotation. A method of combinatorial synthesis of organic molecules is also disclosed.

Abstract: In accordance with the objects outlined above, the present invention provides sensor arrays for the detection of target analytes. The sensor arrays comprising a substrate comprising a surface comprising discrete sites, each discrete site comprising a solvatochromic dye and at least one micro-environment moiety (MEM), both of which are preferably covalent attached to the discrete site. In some aspects, the discrete sites comprise microspheres to which the dyes and MEMs are attached, again, preferably covalently. The dye(s) and MEM(s) at each site can be independently attached, or they can be co-attached using a linker.

Abstract: The present invention relates to novel dihydroisoquinolinone (DHQ) derivative compounds of the following formula: wherein R1 to R7, X, Y, Z, b, c and d have the meanings provided herein. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing DHQ derivative compounds.

Abstract: The present invention provides the synthesis of heterocyclic compounds based on the isoquinoline ring. More specifically, the invention provides novel isoquinoline derivatives as well as novel libraries comprised of such compounds.

Abstract: An apparatus for high-throughput combinatorial syntheses of organic molecules including a reaction vessel for containing a combinatorial-chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis of rotation. A method of combinatorial synthesis of organic molecules is also disclosed.

Abstract: An apparatus for high-throughput combinatorial syntheses of organic molecules including a reaction vessel for containing a combinatorial-chemistry synthetic reaction, a liquid dispenser for dispensing the liquid, a liquid aspirator and an adjustment mechanism. The reaction vessel includes an ingress aperture allowing a liquid to enter into an interior of the vessel and an egress aperture for aspirating the liquid from the vessel. The liquid dispenser dispenses liquid through the ingress aperture. The liquid aspirator aspirates liquid through the egress aperture and includes a rotor for carrying the vessel and orbiting the vessel about an axis of rotation. The rotor is oriented generally in a horizontal plane and includes an adjustment mechanism for adjusting the angle of the vessel relative to the horizontal plane in response to the centrifugal force generated by orbiting the vessel about the axis of rotation. A method of combinatorial synthesis of organic molecules is also disclosed.

Abstract: A technique is disclosed for generating nonrandom combinatorial libraries on solid phase supports in which each of a set of predetermined species of test compounds is present on a predetermined number of solid phase supports, preferably on only one, and each solid phase support has only a single species of test compound. Each of the predetermined species of test compounds is prepared with absolute certainty because the technique does not employ any random division of the solid phase supports. Rather, the method is based on the stepwise division of a continuous solid phase support matrix prior to each synthetic step in which more than one type of subunit is added. Non-limiting examples of matrices of the solid phase supports include polypropylene membranes, polytetrafluoropropylene membranes and cotton thread. The combinatorial libraries made by the technique are also disclosed.

Abstract: A simple, efficient apparatus and method for separation of solid and liquid phases useful in methods of high-throughput combinatorial organic synthesis of large libraries or megaarrays of organic compounds is disclosed. The apparatus and method are useful, whether as part of an automated, robotic or manual system for combinatorial organic synthesis. In a preferred embodiment, an apparatus and method of removal of liquid phase from solid phase compatible with microtiter plate type array(s) of reaction vessels is disclosed.

Abstract: The invention relates to libraries of synthetic test compound attached to separate phase synthesis supports. In particular, the invention relates to libraries of synthetic test compound attached to separate phase synthesis supports that also contain coding molecules that encode the structure of the synthetic test compound. The molecules may be polymers or multiple nonpolymeric molecules. Each of the solid phase synthesis support beads contains a single type of synthetic test compound. The synthetic test compound can have backbone structures with linkages such as amide, urea, carbamate (i.e., urethane), ester, amino, sulfide, disulfide, or carbon--carbon, such as alkane and alkene, or any combination thereof. Examples of subunits suited for the different linkage chemistries are provided.

Abstract: The present invention is directed to a novel "handle" for solid phase peptide synthesis. The handles can be converted from a stable form to a labile form, allowing for cleavage of a peptide amide from the support after synthesis under mild conditions, and after deprotection of the amino acid side chains. The handles are based on a substituted benzhydrylamine skeleton.

Abstract: The invention provides compounds which specifically inhibit factor Xa activity. The compounds consist of the structure X.sub.1 -YIR-X.sub.2, wherein X.sub.1 is H, acyl, alkyl, acylalkyl, arylalkyl or one or more amino acids, and X.sub.2 is a modified C-terminal group, one or more carboxy-protecting groups or one or more amino acids or other substituent, and Y, I and R are tyrosine, isoleucine and arginine, respectively, or peptidomimetic or organic structures that possess the same functional activity as Y, I and R, respectively. In addition, the present invention provides a compound having the structure A1-A2-(A3).sub.m --B, where m is 0 or 1. A compound of the invention can be linear or cyclic and can be about 2 and 43 residues in length. A compound of the invention is characterized, in part, in that it exhibits a specific inhibition of factor Xa activity with a K.sub.i of .ltoreq.100 .mu.M, preferably .ltoreq.