Seminars

This talk will describe an approach for synthesizing molecules that have sizes greater than 100 nm and yet are structurally perfectly defined. The approach relies on the selective and covalent reaction of an enzyme domain with an irreversible linker. Fusion proteins containing two or more of the enzyme domains are treated with linkers terminated in two or more of the irreversible inhibitors, leading to the rapid reaction of the partners and efficient assembly of the megamolecule. Several enzyme-inhibitor pairs have been developed, and used to prepare megamolecules that are linear, cyclic, branched, and that have molecular weights greater than 500,000 Dalton, and sizes greater than 100 nm. The talk will describe the use of this approach to create antibody mimics that include multiple affinity domains, including domains having different specificities. Applications of the megamolecule antibodies include enzyme conjugates for localized treatment, for imaging, and for recruitment of T-cells to tumors. These examples demonstrate the many opportunities for creating functionalized molecular scaffolds for a broad range of applications.

Milan Mrksich is the Henry Wade Rogers Professor with appointments in the Departments of Biomedical Engineering, Chemistry, and Cell & Developmental Biology. He served as Northwestern’s Vice President for Research, was the Founding Director of the Center for Synthetic Biology and an Associate Director of the Robert H. Lurie Comprehensive Cancer Center. He earned a BS degree in Chemistry from the University of Illinois and a PhD in Chemistry from Caltech. He then served as an American Cancer Society Postdoctoral Fellow at Harvard University before joining the Chemistry faculty at the University of Chicago in 1996, where he remained until his move to Northwestern in 2011. His honors include the Camille Dreyfus Teacher-Scholar Award, the TR100 Innovator Award, the Arthur C. Cope Scholar Award, the Illinois Bio ICON Innovator Award, the Pittsburgh Analytical Chemistry Award, and election to the American Institute for Medical and Biological Engineering. Dr. Mrksich is a leader in the science and engineering of materials that contact biological environments. His laboratory has pioneered several technologies, including strategies to integrate living cells with microelectronic devices, the SAMDI biochip technology for high throughput experiments, and the megamolecule approach to making synthetic proteins for therapeutic applications.