Biochemistry and Molecular Biology

Charles Jakobsche

Charles Jakobsche, Ph.D.

Organic Chemistry, Medicinal Chemistry, Chemical Biology

Assistant Professor
Carlson School of Chemistry and Biochemistry
Clark University
Worcester, MA 01610-1477

Phone: 508-793-8866
Email: cjakobsche@clarku.edu

Curriculum Vitae
Research Lab Website


Education

Postdoctoral Fellow, Yale University, 2009-2012
Ph.D. Yale University, 2009
B.A. Williams College, 2004

Current Research Interests

In the Jakobsche group, we are interested in organic molecules that have the potential to impact modern medicine. Over the past several decades, chemistry has produced many new medical drugs that have helped treat ailments ranging from infections to cancer, yet there remain many medical problems whose treatment could benefit from new molecular drugs and from an increased understanding of how these molecules interact with biological systems. In the group, we use organic chemistry to synthesize molecules that have the potential to become new drugs. Many of our target molecules are inspired by molecules made by various natural organisms. Using these natural products as starting points, we then attempt to understand how these molecules perform their medical function and use that knowledge to create modified molecules that may have improved medicinal properties. Members of the group learn not only about organic chemistry and chemical synthesis, but also about the interface of chemistry, biology, and medicine.

Molecules like penicillin are examples of organic compounds whose medical properties have changed the world. Functioning as an antibiotic, penicillin is able to stop a wide range of bacterial infections by interfering with the molecular mechanism by which bacteria cells grow their cell walls. Or at least it was able to suppress many bacterial infections decades ago, before several strains evolved mechanisms of resistance that rendered penicillin ineffective. Indeed, there are strains of infectious bacteria - like MRSA and VRE - that have developed resistance to virtually all known antibiotics. We believe that for humans to maintain the upper hand in our continual struggle against bacteria, we must continue to develop new antibiotics. Therefore, in the Jakobsche group, we have selected a few highly promising compounds that have been recently isolated from natural sources and shown initial success suppressing drug-resistant bacterial strains. We intend to develop chemical syntheses of these target molecules. Once we can synthetically access useful quantities of these compounds, we will be able to rigorously prove their molecular structures, provide material for further biological studies, and synthesize similar, but slightly modified molecules that may have higher potency and more optimal medical properties.

Selected Publications

"Overcoming the Inherent Alkylation Selectivity of 2–3-trans-3–4-cis-Trisubstituted Cyclopentanones" M. B. Reardon, G. W. Carlson, C. E. Jakobsche. Synthesis 2014, 46, 387–393

"Exploring Binding and Effector Functions of Natural Human Antibodies Using Synthetic Immunomodulators" C. E. Jakobsche, C. G. Parker, R. N. Tao, M. D. Kolesnikova, E. F. Douglass, D. A. Spiegel. ACS Chem. Biol. 2013, 8, 2484–2492.

C. E. Jakobsche, P. J. McEnaney, A. X. Zhang, D. A. Spiegel. “Reprogramming Urokinase into an Antibody Recruiting Anticancer Agent” ACS Chem. Biol. 2012, 7, 316–321

C. E. Jakobsche, A. Choudhary, S. J. Miller, R. T. Raines. “n→π* Interaction and n)(π Pauli Repulsion Are Antagonistic for Protein Stability” J. Am. Chem. Soc. 2010, 132, 6651–6653

C. E. Jakobsche, G. Peris, S. J. Miller. “Functional Analysis of an Aspartate-Based Epoxidation Catalyst with Amide-to-Alkene Peptidomimeic Catalyst Analogues” Angew. Chem., Int. Ed. 2008, 47, 6707–6711

A. Voutchkova, D. Gnanamgari, C. E. Jakobsche, C. Butler, S. J. Miller, J. Parr, R. H. Crabtree. “Selective Partial Reduction of Quinolines: Hydrosilation versus Transfer Hydrogenation” J. Organomet. Chem. 2008, 693, 1815–1821

G. Peris, C. E. Jakobsche, S. J. Miller. “Aspartate-Catalyzed Asymmetric Epoxidation Reactions” J. Am. Chem. Soc. 2007, 129, 8710–8711

J. H. Markgraf, A. D. Dowst, L. A. Hensley, C. E. Jakobsche, C. J. Kaltner, P. J. Webb, P. W. Zimmerman “A Versatile Route to Benzocanthinones” Tetrahedron, 2005, 61, 9102–9110