Category: Front Page
A publication from the research group of Professor Adrian Whitty has been selected by the Journal of Biological Chemistry (JBC) as “Paper of the Week.” This distinction is conferred upon JBC papers that the Associate Editors and Editorial Board Members consider to represent the “top 2% of JBC papers in overall importance.” The paper, “Quantitative Analysis of Receptor Tyrosine Kinase-Effector Coupling at Functionally Relevant Stimulus Levels,” provides a rare, quantitative view of how activation of a growth factor receptor is linked to signaling and function. The work is significant because it sheds new light on some of the factors that determine what concentration of growth factor is required to achieve a functional response, and how this functional sensitivity relates to the dose-response behavior observed for receptor activation and for intracellular signaling events. The paper also shows that experiments done using high ligand concentrations can obscure quantitative features of receptor signaling. The journal will publish a profile of the paper’s first author, 5th year graduate student Simin Li (pictured). Other Whitty group investigators who contributed to the work include Dr. Devayani Bhave and Dr. Thomas Riera (former Postdoctoral Fellows), Jennifer Chow and Mariya Atanasova (graduate students), Simone Rauch (undergraduate student), and Dr. Richard Cate (Visiting Scientist).
The high-impact science journal, Nature Chemistry, has published a paper by Professor John A. Porco, Jr., and his colleagues reporting on “Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer” (2 February 2015). Rugulotrosin A is a symmetric dimer isolated from an uncharacterised species of Penicillium. The compound displays significant antibacterial activity against a wide range of Gram positive bacteria. Investigating this important compound, the project was conceived by former Porco Group graduate student, Dr. Tian Qin (now a Postdoctoral Associate in the Baran Laboratory at Scripps Research Institute) and Professor Porco. Collaborators for the project included Professor Richard P. Johnson and his colleague Sarah L. Skrabe-Joiner at the University of New Hampshire (Durham, NH) who performed computational studies and Professor Robert J. Capon and Dr. Zeinab Khalil of the Institute of Molecular Bioscience at the University of Queensland (Australia) who carried out natural extract comparisons and biological studies.
Overall, the project team developed a concise, atropselective approach to rugulotrosin A and stereoisomers through point-to-axial chirality transfer which facilitated determination of the absolute configuration of rugulotrosin A. Computational studies modelling the geometry of intermediate diaryl Pd(II) complexes provided a rationale for the atropselectivity observed in the key Suzuki dimerization. Through HPLC analysis of fungal extracts and synthetic samples, it was determined that Penicillium nov. sp. (MST-F8741) generates rugulotrosin A in an atropselective manner. Moreover, the atropisomers and enantiomers of rugulotrosin A were found to have different activities against Gram-positive bacteria, illustrating the importance of stereochemistry on target selectivity.
The cornerstone of organic synthesis is the development of novel chemical methodology that addresses key limitations in efficiency and reactivity. These synthetic methodologies are best demonstrated in the synthesis of biologically relevant molecules such as current drugs and compounds of study. The goal of this 5-year NIH-funded research program being conducted by Professor Scott Schaus and his Group is to develop operationally simple, highly effective methods for constructing building blocks using boron-containing carbon compounds.
The unique properties of boron and the ability to activate organic boronates to deliver carbon nucleophiles has yielded an impressive array of chemical methods and processes. The Schaus Research Laboratory will extend the ability of organoboranes and boronates to deliver carbanion equivalents in novel condensation reactions including chemoselective carbonyl condensations and multicomponent reactions. The reactions will be rendered asymmetric through the development of asymmetric catalysts and chiral boronate reagents and the utility of the methods developed demonstrated by the asymmetric synthesis of pharmaceuticals and natural products. The majority of top selling drugs are sold as a single enantiomer or isomer. The asymmetric construction of pharmaceuticals becomes increasingly more challenging. As it becomes a greater health concern, so will the need for novel methods and chemical substances that prevent and treat human disease.
Mr. Chao Qi is the recipient of the 2015 Vertex Scholar Award. He is a 4th year graduate student in the group of Prof. John A. Porco. Chao was selected based on his demonstrated excellence in organic chemistry. He has developed extremely elegant and enabling synthetic methodology towards two different natural products, making reactions work, and building complex natural product architectures. Highly productive, he has two major publications, with a third manuscript nearing completion. In addition, Chao plays a leadership role in the Porco laboratory and is currently mentoring an undergraduate researcher.
The 2015 award is made possible by Vertex Pharmaceuticals which has 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.
The Junior Faculty Fellows program of Boston University’s Rafik B. Hariri Institute for Computing and Computational Science & Engineering was established in 2011 both to recognize outstanding junior faculty at Boston University working in diverse areas of the computational sciences, as well as to provide focal points for supporting broader collaborative research in these areas at BU and beyond. Junior Fellows are selected by the Hariri Institute Executive Steering Committee based on nominations received each spring, and are appointed for a two-year term. Each Fellow will give a Hariri Institute Distinguished Lecture.
Chemistry’s Professor Ksenia Bravaya was named one of the four faculty selected as a Fellow for the 2014-2016 term. Professor Bravaya joined the Department of Chemistry in 2013. Her research focuses on state-of-the-art applications and fundamental studies of the microscopic processes at the heart of bio-imaging of cellular processes and excited state reactions, as well as on the development of new quantum chemical computational methodology aimed at addressing unsolved critical challenges in the simulation of a wide variety of excited electronic state processes in complex systems.
Professor Lawrence Ziegler, Chemistry Department Chair, describes her as “a Theoretical and Computational Chemist of national standing and a rising star in the international community,” adding that “given her strong upward trajectory in highest quality research productivity and her pivotal role in developing University Research initiatives in computational materials science, it is no surprise that she has received this honor to be a Hariri Junior Faculty Fellow. She will be an excellent ambassador for Computational Science.“
The newly configured Center for Molecular Discovery (CMD) builds on the legacy of Boston University’s NIH-funded Center of Excellence, the Center for Chemical Methodology and Library Development (2002-2007 and 2008-2013) to create a new functional core with a focus on the development of small molecule probes and therapeutic leads.
Integrating its small molecule screening collection and medicinal chemistry capabilities with the efforts of high-impact researchers in the biomedical field, the CMD is an enabling core resource for advancing translational science at Boston University.
The CMD will continue to engage in high-throughput screening (HTS) and medicinal chemistry collaborations with external researchers as part of the Chemical Library Consortium (CLC) network formed by the CMLD. The Center has new and ongoing collaborations with several research groups on the BU Charles River Campus, the BU School of Medicine, and the National Emerging Infectious Diseases Laboratories. While some of these collaborations are in early stages, others have progressed to the point of early proposal development, proposal submission, and extramural funding. The CMD has also developed collaborations with companies (e.g., Cubist, AstraZeneca, and Vertex) and scientists at other research universities to further leverage its compound collection.
Among the most important forensic evidence that can be collected at a crime scene are body fluids. The National Institute of Justice (NIJ) has funded Prof. Lawrence Ziegler and his group to develop a novel detection and identification platform for these fluids based on the optical methodology, Surface Enhanced Raman Spectroscopy (SERS).
The purpose of this research is to learn about the fundamental capabilities of SERS for detecting, identifying, and characterizing trace amounts of body fluids as a new forensics tool. The investigators believe that development of this optical methodology will lead to a single instrumental platform for the rapid, sensitive, easy-to-use, cost-effective, on-site, non-destructive, detection and identification of human body fluids at a crime scene. No such platform is currently available for this purpose. The successful development of their SERS technology could be transformative allowing the identification of the type of biological materials/fluids with minimal destruction to evidence samples at crime scene locations or from evidence taken from crime scenes. Due to the sensitivity of SERS, suspected human body fluid samples that may be invisible to the eye (but may be evident with the aid of alternate light sources), may be identified leaving sufficient quantity for subsequent DNA analysis. In forensic lab settings, SERS can be used to identify the original body fluid at the time of genetic analysis. The molecular basis for these characteristic SERS signatures will b determined. In addition, SERS can determine the age of some biological stains and corresponding time since a violent crime. Thus, these SERS measurements have the capability to inform criminal investigation directions prior to traditional confirmatory laboratory testing.
This project leverages the Ziegler group’s expertise developed for other SERS-based bioanalytical applications. At the end of this award period, all the elements for an integrated SERS-based, portable trace body fluid detection and identification platform (sample preparation protocols, spectral reference library, software procedures) will be available for field deployment and testing.
Professor Sean Elliott and his group have received funding from the Department of Energy’s Office of Science for their project, “Tuning directionality for CO2 reduction in the oxo-acid: ferredoxin superfamily.” Their aim is to provide a unique, molecular perspective on how electron transfer processes are coupled to catalytic processes that can either be oxidations that liberate CO2, or reductive reactions that capture CO2.
Developing catalytic chemistry for bioenergy production requires a detailed understanding of the molecular mechanisms of multi-electron redox processes, particularly those that transform/capture CO2, producing molecules useful as fuel sources or chemical feed stocks. Understanding the molecular details of how multi electron catalysis can be achieved is a