Purdue Research Foundation

Cornell University

Other

Mediquest Therapeutics, Inc.

University of Michigan

Louisiana State University and Agricultural & Mechanical College

Blinkbio, Inc.

Oridigm Corporation

Donald E Bergstrom

Francis Barany

Sarah Filippa Giardina

Maneesh Pingle

Mark R Burns

Christine L O'Day

Nicolaas M J Vermeulin

Heather K Webb

Lee Daniel Arnold

Jianying Luo

Marilyn Khanna

Philip C Andrews

Ruthann Nichols

Peiming Zhang

Robert P Hammer

Joseph Paul Robinson

Ernest Rowland Blatchley, Iii

Lian-Shin Lin

Shiyue Fang

Dennis Anthony Lyn

Yousheng Guan

Chengyue Shen

Zorana Naunovic

Joseph P Day

Kathyrn E Ragheb

Gerald J Gregori

Sarah Filippa Gardina

Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

Monomers capable of dimerizing in an aqueous solution, and methods of using same

Described herein are silyl monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. Such multimer forming associations of monomers may be promoted by the proximal binding of the monomers to their target biomolecule(s). In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

Silyl monomers capable of multimerizing in an aqueous solution, and methods of using same

The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes a diversity element which potentially binds to a target molecule with a dissociation constant of less than 300 &#x3bc;M and a linker element connected to the diversity element. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to said diversity element, and is capable of forming a reversible covalent bond or non-covalent interaction with a binding partner of the linker element. The monomers can be covalently or non-covalently linked together to form a therapeutic multimer or a precursor thereof. Also disclosed is a method of screening for therapeutic multimer precursors which bind to a target molecule associated with a condition and a method of screening for linker elements capable of binding to one another. The present invention additionally relates to a therapeutic multimer, which includes a plurality of covalently or non-covalently linked monomers, therapeutic monomers, and uses of such dimers and monomers.

Coferons and methods of making and using them

The present invention is directed to a monomer useful in preparing therapeutic compounds. The monomer includes one or more pharmacophores which potentially binds to a target molecule with a dissociation constant of less than 300 &#x3bc;M and a linker element connected to the pharmacophore. The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to the pharmacophore.

A monomer useful in prepa&#x3c0;ng therapeutic compounds includes a diversity element which potentially binds to a target molecule with a dissociation constant of less than 300 11 M and a linker element connected to the diversity element The linker element has a molecular weight less than 500 daltons, is connected, directly or indirectly through a connector, to said diversity element, and is capable of forming a reversible covalent bond or noncovalent interaction with a binding partner of the linker element The monomers can be covalently or non-covalently linked together to form a therapeutic multimer or a precursor thereof.

A method for photochemical reactor characterization includes an application of using dyed microspheres exposed to UV irradiation under a collimated-beam system. Particle specific fluorescence intensity measurements are conducted using samples form the collimated beam and flow-through reactor results using flow cytometry. A numerical model may be used to simulate the behavior of the reactor system to provide a particle-tracking algorithm to interrogate the flow and intensity field simulations for purposes of developing a particle specific estimate of the dose delivery. A method for measuring UV dose distribution delivery in photochemical reactors is provided that includes introducing microspheres labeled with a photochemically-active compound in a UV reactor. The labeled microspheres are harvested downstream of the irradiated zone of a UV reactor and exposed to UV irradiation under a collimated beam of UV irradiation. The method further includes quantifying a UV dose-response behavior, conducting fluorescence intensity measurement on the labeled microspheres from the UV reactor, and developing an estimate of a dose distribution delivered by a UV reactor based on the numerical deconvolution of the sum of the UV dose response behavior and fluorescent intensity of exposed microspheres.

Dyed microspheres for characterization of photochemical reactor behavior

Ligase detection reaction is utilized to distinguish minority template in the presence of an excess of normal template with a thermostable ligase. This process can be carried out with a mutant ligase, thermostable ligase, or a modified oligonucleotide probe. This procedure is particularly useful for the detection of cancer-associated mutations. It has the advantage of providing a quantitative measure of the amount or ratio of minority template.

High fidelity detection of nucleic acid differences by ligase detection reaction

Novel inhibitors of polyamine transport having inhibition constants two orders of magnitude lower than those of known compounds are disclosed. These polyamine analogues are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. Novel chemical synthetic methods to obtain polyamine analogues are disclosed, including the production of a combinational polyamine library. These approaches yield analogues with desirable activities both for diagnostic and research assays and therapy. The assays of the invention are useful for high throughput screening of targets in the discovery of drugs that interact with the polyamine system.

Polyamine analogues as therapeutic and diagnostic agents

Novel inhibitors of polyamine transport having inhibition constants two orders of magnitude lower than those of known compounds are disclosed. These polyamine analogues are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. Novel chemical synthetic methods to obtain polyamine analogues are disclosed, including the production of a combinatiorial polyamine library. These approaches yield analogues with desirable activities both for diagnostic and research assays and therapy. The assays of the invention are useful for high throughput screening of targets in the discovery of drugs that interact with the polyamine system.

The present invention provides a method for identifying one or more low abundance sequences differing by one or more single-base changes, insertions, or deletions, from a high abundance sequence in a plurality of target nucleotide sequences. The high abundance wild-type sequence is selectively removed using high fidelity polymerase chain reaction analog conversion, facilitated by optimal buffer conditions, to create a restriction endonuclease site in the high abundance wild-type gene, but not in the low abundance mutant gene. This allows for digestion of the high abundance DNA. Subsequently the low abundant mutant DNA is amplified and detected by the ligase detection reaction assay. The present invention also relates to a kit for carrying out this procedure.

Coupled polymerase chain reaction-restriction-endonuclease digestion-ligase detection reaction process

Novel &ldquo;bispolyamine&rdquo; inhibitor compounds of polyamine transport are disclosed. These compounds are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. These compounds display desirable activities both for diagnostic and research assays and therapy.

Thermostable DNA ligase mutants

Oligonucleotides having at least ten nucleosides, at least two of which are selected from the group consisting of A, T, C and G, and at least one nucleoside being a universal nucleoside of the formula: ##STR1## wherein: each R.sub.n is H, OH, F or OCH.sub.3 ;

Growing community of inventors

West Lafayette, IN, United States of America

Donald E Bergstrom