Tagged: John Porco
The Porco Research Group has received a 4-year, $1.2 million award from the National Institutes of Health for their proposal, Chemical Synthesis of Bioactive Flavonoid and Xanthone-Derived Natural Products.
Undertaken in conjunction with biological collaborators, including Professor Tom Gilmore (BU Biology) and Dr. John Beutler of the National Cancer Institute’s Center for Cancer Research, the goal of the research is to develop new chemical methodologies to enable the synthesis of bioactive flavonoid and xanthone-derived natural products that could lead to biologically active antitumor and anti-infective agents. Specifically, such agents will be useful as novel pharmacological therapies and as cytotoxic agents against both human cancers and malaria.
Their aims include total syntheses of anticancer agents such as the kuwanons and related prenylflavonoid Diels-Alder natural products as well as the bioactive tetrahydroxanthones blennolides A and B.
The award enables an exciting new research direction for Professor Porco and his collaborators involving the use of nanoparticles in organic reactions, asymmetric catalysis, and novel cycloaddition strategies.
The recipient of this year’s Vertex Scholar Award is Tian Qin, a third year student in the Professor John Porco’s Research Group. His selection was based on his development of an extremely elegant and enabling synthetic methodology towards a very difficult series of natural product targets with anticancer and cytotoxic activity. This work was recently published as a Communication in the Journal of the American Chemical Society. His contributions to student mentoring are also recognized by his selection for this award award. Tian came to BU in 2008 from the Graduate University of the Chinese Academy of Science, where he majored in organic materials in chemistry.
The 2011 award is made possible by Vertex Pharmaceuticals who have provided this generous graduate fellowship in organic chemistry for an exceptional 2nd, 3rd or 4th year graduate student in our Ph.D. program. The BU-Vertex Educational Partnership Program, established in 2010, offers scholarships funded by Vertex Pharmaceuticals, a biotechnology company based in Cambridge, Massachusetts, US.
Each award funds a student’s stipend, fees, and research supplies for one year. The Vertex program is an important unencumbered gift to BU Chemistry. As part of its aim to promote cooperation between industry and academia, Vertex provides the Scholars with access to mentoring from their scientists. Vertex, with a market capitalization of more than $7.2 billion, is committed to the discovery and development of breakthrough small-molecule drugs for serious diseases.
Christina Rodrigo Receives American Cancer Society Postdoctoral Fellowship.
The goal of the American Cancer Society (ACS) fellowships is to provide talented postdoctoral research associates funding that will lead to an independent career in cancer research. This Fall, Christina Rodrigo, a postdoctoral research associate in the Porco Group received one of these highly sought national awards for her proposed work on silvestrol, a rocaglate derivative isolated from the plant Aglaia foveolata. Silvestrol has been shown to have potency against breast, lung, and prostate cancer cell lines and chronic lymphocytic leukemia B cells but little is known about about its mechanism of action.
Dr. Rodrigo’s goal is to synthesize molecules similar to silvestrol with slight modifications, and to study and compare these molecules to silvestrol to learn more about how silvestrol works as a treatment for cancer. In addition to the excellence of her proposed research and demonstrated productivity, another contributing factor for her receipt of the ACS Fellowship is the quality of the training and mentoring that she receives from Professor Porco and his Group.
There are many medically important drug targets that current drug discovery technology is not able to address. Collaborative basic research in Chemistry, Biology, and Biochemistry is key to solving these intractable problems to enable the discovery of new classes of drugs. A multidisciplinary team at Boston University, led by Associate Professor of Chemistry Adrian Whitty, aims to develop new approaches for challenging molecular targets. The National Institute of General Medical Sciences awarded this team a 4-year, $1.6 million grant entitled Design of Macrocyclic Inhibitors of the NEMO/IKKα/β Protein-Protein Interaction.
Only about 10% of the potential drug targets in the human genome have been successfully targeted with marketed drugs. Of the remaining 90%, many are intracellular proteins whose function is critically dependent on their reversible interactions with other proteins. Despite decades of effort by the pharmaceutical industry, developing oral drugs that inhibit protein-protein interactions (PPIs) has rarely succeeded and has become recognized as a major scientific and technological challenge.
The primary goal of this project is to determine whether the use of a class of natural product-inspired compounds called macrocycles constitutes a broadly applicable method for developing oral drugs against PPI targets. As a first challenge, the team is attempting to develop macrocycles that block the activity of NEMO, a key component of the IKK complex that activates NF-κB signaling. Chronic hyperactivity of the NF-κB pathway is associated with many human inflammatory diseases and cancers. Thus, the development of drug-like inhibitors of this pathway is highly relevant to public health.
The work will determine whether appropriately designed synthetic macrocycles can inhibit PPI targets while maintaining good drug-like properties. In terms of NF-κB and disease, their work will provide a means for testing whether inhibiting the interaction of NEMO with IKK—as a more targeted alternative to completely ablating all IKK activity—represents a useful new approach for attenuating inflammation.
In addition to Professor Whitty (quantitative biochemistry and drug discovery), the multidisciplinary research team comprises Professors Sandor Vajda and Dima Kozakov (computational chemistry), John Porco and Aaron Beeler (macrocycle synthesis), Karen Allen (X-ray crystallography), and Tom Gilmore (NF-κB pathway biology).
The Ignition Award Program provides funds to evolve BU research to the stage where it can be licensed, form the basis of a new company, or be used to create a new, non-profit social enterprise. In June 2010, two Chemistry faculty, John Porco and John Snyder, received these highly competitive awards for their respective commercially promising projects.
Professor Porco’s research is the “Development of Novel Protein Synthesis Inhibitors as Chemotherapeutic Agents.” The work will involve synthesis of novel silvestrol (rocaglate) derivatives and their evaluation as protein translation inhibitors in the Pelletier laboratory at McGill University. Promising derivatives will be tested in the National Cancer Institute’s 60 cancer cell line panel and then advanced to animal models for B-cell leukemias and other cancers that are highly susceptible to translational control.
Professor Snyder’s research focuses on the “Development of New Anti-Tuberculosis Agents.” Three synthetic compounds from the Center for Chemical Methodology and Library Development (CMLD-BU) were determined to be “hits” against Mycobacterium tuberculosis, the tuberculosis-inducing microorganism. The preliminary biological activity data against M. tuberculosis, coupled with the unique structures of the lead compounds have justified advancing these compounds toward commercialization through the biological assays needed to establish the scope of activity and bioavailability.
Professor John Porco and his group have received a 4-year, $1.6 million award (2010 to 2014) to develop and refine biomimetic syntheses using copper-mediated enantioselective oxidation processes; photochemical cycloaddition employing excited state intramolecular proton transfer (ESIPT); and asymmetric reactions of acylphloroglucinols. Professor Porco and colleagues are applying these methodologies to synthesize complex natural products, including bisorbicillinol, sorbicillactone A, aglaiastatin, ponapensin, and myrtucommulones A and B. Collaborating with the Porco Group is Prof. Linda Doerrer who is performing mechanistic investigations to understand copper-mediated enantioselective oxygenase and oxidase processes and also develops catalytic, asymmetric oxidation processes. Likewise, a continuing collaboration with Professor Eric N. Jacobsen and coworkers (Harvard University) seeks to identify chiral thiourea photocatalysts for asymmetric photocycloadditions. More
Professor John A. Porco, Jr. has received the distinguished 2003 Bristol-Myers Squibb (BMS) Award in Synthetic Organic Chemistry. The grant provides a total of $300,000 of unrestricted research support over a three-year period and is one of only two given by BMS worldwide each year to support the academic research community.
The award acknowledges the outstanding record of achievement of Professor Porco and his research team in the field of synthetic organic chemistry. Synthetic organic chemistry has long been a critical tool in the drug discovery efforts of pharmaceutical companies and biotechnology firms. Research in the Porco laboratory focuses on the development of new synthetic methodology for the efficient chemical synthesis of complex molecules and the utilization of parallel (or combinatorial) synthesis techniques towards the synthesis of complex chemical libraries.
Recent total synthesis accomplishments include the synthesis of the salicylate enamide natural products lobatamide C and oximidine II, and the epoxyquinoid natural products torreyanic acid, epoxyquinol A, and panepophenanthrin. The Porco team recently employed parallel synthesis approaches to prepare complex spiroketal libraries and highly functional angular structures from epoxyquinol dienes. Professor Porco is the Director of the new Center for Chemical Methodology and Library Development at Boston University (CMLD-BU).