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Kwon S.J.,The Interdisciplinary Center | Mora-Pale M.,The Interdisciplinary Center | Lee M.-Y.,Solidus Inc. | Dordick J.S.,The Interdisciplinary Center | Dordick J.S.,Rensselaer Polytechnic Institute
Current Opinion in Chemical Biology | Year: 2012

The enormous pool of chemical diversity found in nature serves as an excellent inventory for accessing biologically active compounds. This chemical inventory, primarily found in microorganisms and plants, is generated by a broad range of enzymatic pathways under precise genetic and protein-level control. In vitro pathway reconstruction can be used to characterize individual pathway enzymes, identify pathway intermediates, and gain an increased understanding of how pathways can be manipulated to generate natural product analogs. Moreover, through in vitro approaches, it is possible to achieve a diversification that is not restricted by toxicity, limited availability of intracellular precursors, or preconceived (by nature) regulatory controls. Additionally, combinatorial biosynthesis and high-throughput techniques can be used to generate both known natural products and analogs that would not likely be generated naturally. This current opinion review will focus on recent advances made in performing in vitro pathway-driven natural product diversification and opportunities for exploiting this approach for elucidating and entering this new chemical biology space. © 2012 Elsevier Ltd. Source

Samsung and Solidus Inc. | Date: 2012-05-17

There is provided a fluid discharging device including: a first pressure generating unit generating a first pressure for discharging a fluid; a second pressure generating unit generating a second pressure for discharging a fluid, and being controllable so as to change a magnitude of the second pressure; and a nozzle discharging the fluid pressurized by the first and second pressure generating units.

Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase II | Award Amount: 500.00K | Year: 2009

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). This Small Business Technology Transfer (STTR) Phase II project will address further development and commercialization of a multi-enzyme lead optimization chip (Multizyme Chip) for high-throughput generation of lead compound analogs coupled with cell-based screening for the rapid identification of biologically active derivatives. Such a capability directly impacts a key bottleneck in drug discovery; namely, the efficient optimization of lead compounds to develop drugs with optimal pharmacological properties. Solidus Biosciences, Inc. proposes to combine six biocatalysis with pharmacological screening to provide rapid identification of biologically active compounds against cell-specific targets, which is a new paradigm for lead optimization. Moreover, the Multizyme Chip platform will be well-suited for lead optimization in related industries, including agrochemicals, cosmetics, and cosmeceuticals. The Solidus technology will thus improve the competitiveness and efficiency of the pharmaceutical, cosmetics, and chemical industries, and will serve as a rich source of new and improved commercial products. The broader impacts of this research are the advances that Solidus Biosciences will achieve toward generating better and safer drugs, reducing the cost to develop these drugs, and increasing the overall efficiency of the pharmaceutical industry. Solidus will generate Multizyme Chips for purchase by pharmaceutical and biotechnology companies to facilitate their lead optimization programs, particularly those involving natural product-derived and complex synthetic small molecule leads. Cryopreservation techniques developed in Phase II will enable the sale of chips and chip-handling devices produced during Phase I, and will allow seamless penetration of the Solidus technology platform into the company's target markets.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 200.00K | Year: 2007

DESCRIPTION (provided by applicant): The proposed research program applies Solidus technology in microarraying, biocatalysis, and screening and the Linhardt group's expertise in heparin/heparan sulfate to the field of glycomics. Glycomics, the comprehensive study of glycan structure-function relationship, is a sub-discipline of metabolomics and the next step beyond genomics and proteomics. Heparin glycosaminoglycans (heparin and heparan sulfate) are among the most structural complex biopolymers. These glycans carry and store significant biological information crucial in virtually all pathological and pathophysiological processes involving cell-cell interaction and communication. The specific aims and milestones of this Phase I STTR proposal are to: 1. prepare a heparin glycan microarray; 2. probe this microarray with the highly specific heparin-binding protein, antithrombin III; 3. prepare an enzyme-modified heparosan microarray; 4. probe this microarray with a collection of heparin-binding proteins to examine binding specificity; and 5. prepare a structurally defined glycan microarray based on the glycosyltransferase extension, and enzymatic modification of heparosan oligosaccharide acceptors for probing with heparin-binding proteins. Phase I will focus on developing the core technology required for developing a HepGly chip as a glycomics platform for screening interactions with heparin-binding proteins. Potential applications for a HepGly microarray include the development of the next generation of heparin-based drugs, the evaluation small molecule drugs that antagonize with heparin/heparan sulfate interaction with heparin-binding proteins and the rapid screening of biological samples in diagnostic applications. A phase II proposal will be prepared to develop these commercial applications.

Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase I | Award Amount: 150.00K | Year: 2007

This Small Business Technology Transfer (STTR) Phase I research project aims to develop a new method for generating lead compounds by using enzymatic modification of compound sets.Availability of new methodology to generate biologically active compounds from existing molecules may enhance the success of the drug discovery process and may lead to the discovery of new and useful therapeutics.

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