Research Overview: Professor Jakobsche brings a wide range of interests and expertise to his research. The group’s research projects typically embody the following major themes:
Antibiotics Project: Penicillin, the molecule drawn on the top of this page, is one example of an organic molecule 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 render penicillin ineffective. Indeed, there are strains of infectious bacteria – like MRSA and VRE – that have developed drug-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. We have identified a highly promising compound that has been recently isolated from a natural source and shown initial success killing drug-resistant bacterial strains. We are develop a route to make this molecule through organic synthesis. Once we can synthetically access useful quantities of this compound, we will be able to rigorously prove its molecular structure, provide material for further biological studies, and synthesize similar, but slightly modified molecules that we expect to have higher potency and more optimal medical properties.
Cancer Metastasis Project: Cancer is the second most deadly disease in America today, with the late-stage, invasive cancers being the most severe and difficult to treat. It is currently estimated that approximately 40% of Americans will develop invasive cancer at some point in their lives. As healthy human cells change into cancerous cells and then into invasive metastatic cancer cells, they undergo a series of biochemical changes that create the cancerous and metastatic phenotypes. By understanding process of cancer metastasis, scientist have identified particular enzymes and biochemical pathways that cause metastasis of cancer cells. Working in collaboration with Professors Fred Greenaway and Sharon Huo here at Clark, we hope to develop organic molecules that can inhibit some of these enzymes and pathways and thereby block cancer cells from migrating. We use a combination of organic synthesis, biochemistry, and chemical biology to move towards developing potent enzyme inhibitors that can provide more precise knowledge about the biology of cancer metastasis and serve as pre-clinical leads for new anti-cancer medicines.
Activity–Based Protein Profiling Project: The field of chemical biology uses organic chemistry to manipulate and study biological systems. Activity-based protein profiling uses synthetic molecular probes to interact with families of proteins and allow all the proteins to be simultaneously studied as a group. We have designed and created a new probe molecule that we are using to learn about a family of disease-related proteins and measure how selectively various enzyme inhibitors can bind to a particular protein that we are targeting.
Amyloid Project: Protein misfolding is a process that is not fully understood, yet is critical to numerous diseases including Alzheimer’s disease and Parkinson’s disease. To function properly, proteins fold into well-defined 3-dimensional structures, yet many proteins and peptide fragments are known to self-assemble into amyloid fibrils, which are large insoluble structures that are observed as symptoms for several diseases. In collaboration with Professor Noel Lazo’s group here at Clark, we are designing and making functional organic molecules that can be used to study the structures and modify the properties of disease-related amyloid fibrils.
Radical Project: While organic radicals are often transient intermediates that occur during reactions, some radicals are stable and can be isolated. Some of these stable radicals can be used to initiate chemical reactions, and others have interesting physical properties. In collaboration with Professor Juan Novoa, from The University of Barcelona, and with Professor Mark Turnbull in our department, we are making a type of organic radical molecules that have unique magnetic properties and unexplored chemical reactivity. We aim to better understand these structures and their chemical reactivities.