Category: Snyder, John
The National Science Foundation’s Research Experience for Undergraduates Program supports active research participation by undergraduate students in any of the areas of research funded by the National Science Foundation. For the second time, BU Chemistry has received one of these coveted site awards. Focused on the theme “Fundamental Research in Chemistry Addressing Problems in Biology,” the 3-year program (2012-2015) is led by Professors John Snyder (Principal Investigator) and Linda Doerrer (Co-PI).
BU Chemistry has dramatically improved the undergraduate organic chemistry laboratory by giving students access to major research instrumentation and state-of-the-art technology. By enabling more modern experimentation, these resources foster critical thinking and problem solving skills that prepare undergraduates for graduate and pre-professional schools or for careers in industry. Advanced experimentation also enables more sophisticated student-designed research-type projects.
Renovations and instrumentation
Renovations in the Metcalf Center for Science and Engineering (Summer 2011) have transformed our organic chemistry instructional laboratories into an 6,350 sq. ft. suite with fume hoods and bench areas for each student, auxiliary support space, and a chemical stockroom. Space has been dedicated for an undergraduate instrumentation center for with fully automated high field nuclear magnetic resonance (NMR), ultra-performance liquid chromatography–mass spectrometry (UPLC-MS), Fourier transform infrared spectroscopy (FT-IR), and gas chromatography-mass spectrometry (GC-MS). Microwave reactors allow for rapid reaction rates, enabling multistep syntheses to be undertaken in a single day.
Advanced Technology in the Laboratory Curriculum
The entire laboratory curriculum of our sophomore-level organic chemistry sequence has been transformed with the adoption of the “paperless laboratory” through the use of electronic laboratory notebooks. Spearheaded by Professor John Snyder and Professor Scott Schaus and Postdoctoral Faculty Fellow, Seann Mulcahy, integration of these technology resources have enabled the creation of an open-access repository of laboratory protocols, design of laboratory experiments that facilitate sharing of data between students and between disciplines, exposure to automated NMR, GC-MS, and UPLC-MS, and remote download and manipulation of spectroscopic data.
- Fast Forward to the 21st Century -The new instrumentation advances undergraduate capabilities well beyond those in traditional sophomore organic textbooks that repeat traditional experiments. Instead, we have designed novel, research-oriented, exploratory experiments that have applicability to modern organic chemistry. These include cross-coupling experiments, olefin metathesis, and many others. Experiment protocols are available on BU’s Digital Common site (DCommon), an open-access online repository that is accessible not only by our students, but by outside instructors as well. Users can be granted upload privileges to deposit modified or new protocols thereby creating a rich resource to the worldwide research community. In addition, a DCommon collection of NMR and UPLC-MS spectra is being compiled as a teaching tool for organic chemistry courses.
- Major Instrumentation – BU is unique in using the latest instrumentation for routine, hands-on training at the sophomore level. The laboratory’s state-of-the-art instrumentation also allows comprehensive characterization of synthetic material prepared in each experiment. Students now routinely run 1H and 13C NMR (and 2D COSY), UPLC/MS, GC/MS, and FT-IR on their own samples and to obtain a set of data which approaches the quality needed for publication.
- Into the Cloud – Our students are now using fully electronic laboratory notebooks, which they populate on their laptops with reaction details, procedural notes, and safety protocols. Analytic data and spectra (manipulated and interpreted remotely) are uploaded into the notebook and serve as part of their final laboratory reports.
CMLD-BU researchers Bradley Balthaser, Meghan Maloney, Aaron Beeler, John Porco & John Snyder, in a paper published in the journal Nature Chemistry [23 OCTOBER 2011 | DOI: 10.1038/NCHEM.1178], present a new approach to accessing new, biorelevant structures by “remodeling” natural products. In this case, they demonstrate how the natural product derivative fumagillol can been remodeled to access a collection of new molecules using highly efficient chemical reactions.
Boston University Chemistry has launched a new Digital Common site for organic chemistry teaching lab protocols. According to Prof. John Snyder, “developing a freely accessible, dynamic data base of sophomore organic lab experiments was driven by the reality that we were creating most of our sophomore course labs rather than relying on a lab textbook. In fact, many colleges and universities are doing the same. As PFFs from our department have gone on to faculty positions, the potential for having a large number of talented contributors to the database became rather obvious.” Early users / contributors include PFF alumna Prof. Amy Bradley (Wilkes University) and Prof. Lauren Rossi (Roger Williams University). Instrumental in developing the free access database is current PFF, Dr. Seann Mulcahy.
The BU Digital Common is an open access repository, which means that the full text of the work deposited here is freely accessible to the world via the web. BU Chemistry organic lab instructors have placed protocols developed over the years to be freely and easily accessible to other instructors. Users can download and modify these protocols to use in their own courses as they see fit. Users may also be granted upload privileges to deposit modified or new protocols that will be of use to the world-wide teaching community.
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.
Snyder Recognized for Excellence in Student Advising
For the second year in a row, a member of the Chemistry faculty has received the Templeton Prize for Excellence in Student Advising, the top undergraduate advising award given by the College of Arts and Sciences.
The 2009 recipient is Prof. John Snyder. Despite his busy schedule which involves teaching, research, and management of two NSF summer undergraduate research programs, this dedicated advisor and mentor is always available to meet with undergraduates. One student related that “Anytime I have a problem, personal or academic, Dr. Snyder was right there and took the time to give me advice and help. He even went out of his way to find me a scholarship for the summer so I could take two classes that I wouldn’t have been able to afford otherwise.”
Among many enthusiastic accolades, another student stated: “Being a freshman and ignorant of many aspects of college life, I had trouble adjusting. It was always my dream to enter graduate school one day. However, I really had no clue what to do to get there. I sought the advice of my professors, but Dr. Snyder really helped me the most. He would spend time to get to know me, understand what type of person I am, help me to learn where my strengths and abilities are, and to help me to discover which aspect of chemistry I was most passionate about. In doing so, I personally felt that Professor Snyder went the extra mile to be a part of my academic journey. It is professors like Dr. Snyder that make Boston University such a great school.”
This news item has been adapted from the April 30, 2009, award announcement at the CAS Faculty Meeting. We thank the Associate Dean for Undergraduate Programs, Wayne Snyder, for sharing his citation.
The National Institute of General Medical Sciences (NIGMS) is continuing its support of the CMLD-BU as one of five Centers of Excellence addressing the problem of how to develop small molecule libraries and techniques for making them that meet all the needs of pharmaceutical and biomedical scientists.
The CMLD-BU was originally established in 2002. The renewal is for another 5 years (through 2013) and is worth more than $11.5 million. The first year’s funding, $2.6 million, will be used to develop microfluidics and other strategies to synthesize small molecules for application by the biological community. The program is highly collaborative. Professor John A. Porco, Jr., who is the Director and Principal Investigator, is joined by Co-PI’s Professors Jim Panek, Scott Schaus, John Snyder, and Corey Stephenson, who are leaders in the field of organic chemistry.
The goal of the Center is to develop cutting-edge technologies to generate, analyze, and optimize chemical libraries and synthesize thousands of novel chemical entities using high-throughput techniques. It is also making these methods and libraries broadly available for biomedical research and drug discovery. The CMLD’s PI’s are collaborating with biologist, Professor Tom Gilmore, to determine the physiological activities of new molecules.
CMLD-BU Scientists Awarded National Institutes of Health Grant in Pilot-Scale Libraries for High-Throughput Screening Program
Co-investigators of the Boston University Chemical Methodology and Library Development Center (CMLD-BU) (http://cmld.bu.edu) have been awarded a three-year grant for their joint proposal “Generation of Stereochemically and Structurally Complex Chemical Libraries.” The goal of the work by Professors Porco, and co-Principal Investigators Panek, Schaus, and Snyder, is to generate a number of stereochemically and structurally complex chemical libraries for inclusion in the National Institutes of Health (NIH) Molecular Repository (http://mlsmr.glpg.com/MLSMR_HomePage/index.html). They will develop five library projects that are distinct from ongoing and planned CMLD-BU library projects, but which utilize novel chemistries previously developed in their laboratories. Target pilot libraries include complex dihydropyrimidones, azaphilone-derived libraries, tetracyclic alkaloid-type libraries, exo-methylene scaffolds and derived spirocycles, and macrocyclic lactams. In addition, all planned libraries have been designed to include unique structures that do not overlap in chemical space with molecules currently in the PubChem database. Data will be shared using an internet-based structure-searchable database of synthesis protocols.
The Molecular Libraries and Imaging Initiative is a component of the “New Pathways to Discovery” theme of the NIH Roadmap, which seeks to enable the rapid transformation of new scientific knowledge into tangible benefits for public health. While high-throughput screening (HTS) of small-molecule libraries is widespread in the pharmaceutical industry, the goal of the Molecular Libraries (ML) Roadmap Initiative is to facilitate the use of HTS and chemical libraries within the academic community. It is anticipated that the ML initiative will produce research tools (including novel small-molecule modulators of cellular function and phenotypic assays) to facilitate studies of biology and physiology (http://nihroadmap.nih.gov/molecularlibraries). It is anticipated that the initiative will complement private sector drug development efforts by contributing to the identification and validation of novel drug targets, as well as molecular structure classes with potential for development into therapeutics. The initiative promises benefits to public health, especially for rare or marginalized disorders.