Natural Molecules that Can Improve Health

Efficient chemical synthesis of new and potent bioactive molecules

Nature has created unique molecules that help organisms survive. The properties these molecules possess also have an array of applications for scientists. However, often these precious molecules are difficult to access from natural sources because they are found in very small quantities and the producing organisms are rare and located in remote parts of the biosphere. Dr. Mo Movassaghi, of the Massachusetts Institute of Technology, develops the means to access these structurally complex and potently bioactive molecules. His research allows unique access to rare and potently bioactive small molecules, including natural products, that enables novel chemical and biological investigations aimed at development of new treatments for human ailments such as cancers and autoimmune diseases.

Dr. Movassaghi's research team focuses on the development of concise and unified synthetic strategies, inspired by biogenetic considerations, to readily access these complex molecules, thus enabling their detailed chemical, biochemical, and biological study. Using his organic chemical synthesis approach to access complex alkaloids, an important class of molecules that contain basic nitrogen atoms, his research program provides an unlimited and reliable source for these molecules. Furthermore, Dr. Movassaghi's research enables access to many designed derivatives that cannot be obtained from any natural source, thus enabling logical refinement and improvement of these molecules' desired properties. The Movassaghi Group's ability to conduct precise atomic level molecular editing of these important molecular architectures requires the highest level of precision in chemical manipulation of complex molecules and is made possible by deep understanding of the fundamental chemistry of these molecules. 

 

Current research includes:

  • Dr. Movassaghi is focused on the development of concise chemical synthesis routes to rare and complex bioactive molecules with both relative and absolute streochemical control. Dr. Movassaghi's focus on chemical synthesis enables access to structurally complex and potently bioactive molecules from readily available and simple molecular precursors. His research group's discoveries allow preparation of these molecules in the laboratory using novel and precise molecular transformations. The compounds that are the focus of his research provide significant challenges to existing chemical synthesis methodologies and strategies, thus providing an outstanding platform for the discovery and development of fundamentally important new chemical transformations. Once a versatile strategy for chemical synthesis of the target compound is developed, unprecedented access to the compound along with a diverse collection of related molecules is offered that enables detailed follow up studies in a series of multi-disciplinary and collaborative studies.

 

  • Dr. Movassaghi's research enables the precise study of the complex structure of these molecules. This aspect of the research allows confirmation, assignment, and sometimes revision of the originally assigned molecular structure as demonstrated by several of the Movassaghi group's recent studies. Precise understanding of the molecular structure of bioactive molecules is critically important since a molecule's biological activity is due to specific interaction between its molecular architecture and those of a biological target.

  • Dr. Movassaghi has several established multi-disciplinary collaborations to study, discover, and identify new applications for compounds that are uniquely accessible from his research program. Once Dr. Movassaghi's research provides efficient and robust access to a new compound class, the following detailed chemical and biological studies unravel the critical features of the compounds needed for biological activity and allow synthesis of novel and functional molecules with superior properties. For example, Dr. Movassaghi's efficient laboratory chemical synthesis and study of a compound isolated from a marine sponge by Dr. William Fenical, another Benefunder featured researcher, led to its first chemical synthesis and enabled the detailed chemical and biological evaluation of a portfolio of related compounds accessed in the Movassaghi Group that is providing the foundation for a series of multi-disciplinary studies aimed at discovery and development of new potent anticancer agents and potential antibiotics. 

  • Dr. Movassaghi focuses on chemical synthesis of targets that are selected on the basis of novel molecular architecture, important biological activity, and the potential for mechanistic studies. Dr. Movassaghi identifies structural patterns in the target compounds that are important in offering the observed biological activity. Once scientists know which structural elements are critical in providing the biological activity and what portions of the molecule tolerate changes, a new portfolio of designed and functional derivatives with superior and enhanced activity and function can be synthesized. For example, new molecular entities could be prepared that retain the biological activity and permit molecular linkage to an antibody for delivery to a specific target. The combination of chemical synthesis and biological and mechanistic evaluation of the target molecules enable the discovery and development of potential new highly effective treatments for human ailments.

Bio

Dr. Movassaghi is motivated by the ability of synthetic organic chemists to design and assemble complex molecules with special properties that impact various fields of science including medicinal chemistry, chemical biology, and materials science. The ability to influence matter, with precision at the molecular level, allows the synthesis and preparation of important natural and designed molecules with highly sought after properties.

Dr. Movassaghi finds the insight needed to prepare a given complex molecule requires deep understanding of the fundamental chemistry and physical properties of the target molecule and related intermediates. This insight is critical in synthesis of derivatives of the target and the optimization of the desired properties. Furthermore, synthesis of functional derivatives enables preparation of molecular probes to help elucidate the biological mode of action of the target compound and facilitate application in medicine.  If Dr. Movasssaghi's research team can prepare and access a complex molecule reliably, then they have the opportunity to fully study its structure and properties, thus enabling the logical design of superior derivatives for application for the betterment of the human condition.

The research interests of the Movassaghi Group is synthetic organic chemistry in broad terms, including complex natural product synthesis in concert with the discovery and the development of new reactions for organic synthesis. The group's focus is the synthesis of structurally interesting and biologically relevant natural products that provide a platform for further methodological developments and detailed mechanistic studies. These synthetic efforts are complemented with programs aimed at the development of new transformations for organic synthesis including catalytic and asymmetric processes.

The Movassaghi Group is comprised of highly talented and accomplished young scientists and researchers. The team of approximately a dozen co-workers consists of postdoctoral research fellows, graduate students, undergraduate students, and visiting scholars who have completed their prior education and research experience in many of the world's top universities and research institutions. The Movassaghi research team includes both domestic and international coworkers with a diverse set of expertise. The team has many ongoing research collaborations with clinicians in hospitals, academicians in universities, and research scientists in industry. The Movassaghi Group's research collaborations focus on discovery and development of new and highly potent anticancer small molecules in addition to understanding their mechanism of action to enable novel and superior drug development.

Website: http://web.mit.edu/movassag/www/

Awards

Yoshimasa Hirata Memorial Foundation Gold Medal, Japan, 2011

American Chemical Society Elias J. Corey Award for Outstanding Original Contribution in Organic Synthesis by a Young Investigator, 2010

American Chemical Society Arthur C. Cope Scholar Award, 2009

Recipient of the Alfred P. Sloan Research Fellowship (2008), Camille and Dreyfus Teacher-Scholar Award (2008), NSF-CAREER (2006), Beckman Young Investigator (2006), and Damon Runyon Cancer Research Foundation Scholar (2004)

Awards from industry including Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Merck, Novartis, and Roche

Patents

Compounds, Compositions and Methods of Agelastatin Alkaloids

Movassaghi, M.; Hergenrother, P.; U.S. Provisional Patent Application 61/880,018; filing date September 19th, 2013.

Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

Movassaghi, M.; Boyer, N. C.; Kim, J.; Hergenrother, P.; Morrison, K.; U.S. Patent Application No. 61/733,222; filing date December 4th, 2012.