Emil T. Hofman Professor of Chemistry & Biochemistry; Director, Notre Dame Integrated Imaging Facility
Biological membranes are important not just simply as vessels containing the stuff of life, but they also regulate communication and interaction between cells, their environment, and their organelles. To accomplish this, membranes are incredibly complex, employing hundreds of constituent elements arranged in a fluid mosaic embedded with proteins. The design of molecular probes and drugs which are able to carry out specific tasks at the membrane in spite of this complexity is a formidable challenge for synthetic chemists and demands adaptation of the typical tool sets they employ.
To this end, research in the Smith group is highly interdisciplinary, and it combines the synthesis of novel organic compounds with biochemical and biophysical methods to evaluate their utility. Often we employ supramolecularåÊelements in our compound design. This rapidly growing field is less reliant on strong covalent bonds, but rather engages dozens or even hundreds of weak coordinate bonds to rapidly and firmly hold a target (much as Gulliver bound by the hundreds of ropes of his diminutive Lilliputian captors). Another common design element in our compounds is photophysicalåÊproperties (i.e. fluorescence, photoluminescence, photothermal). These not only give us useful tools to "see" the effect of our molecules in vitro, but also enable potential therapeutic or diagnostic applications in medicine.åÊ
Our past efforts saw the development of small molecules which could transport biomoleculesåÊ(e.g. ions, peptides, catecholamines) through membranes, or which could target or manipulate phosphatidylserine (which is exposed in dying cells and some pathogens). Our more recent work is with a red-fluorescent, supramolecular structure we call Synthavidin. This new technology lets us rapidly assemble a library of molecular probes towards specific biomarkers (e.g. cancer, bone). We can control the ligand density of these probes, which permits us to study multivalency effects on membrane binding and also to quickly screen and identify useful compounds for medical applications.åÊ
- "Smart Molecules for Imaging, Sensing and Heath (SMITH)" Smith, B.D. J. Org. Chem. 2015, 11, 2540-2548.
- "Bacterial Imaging and PhotodynamicåÊInactivation Using Zinc(II)-DipicolylamineåÊBODIPY Conjugates" Rice, D.R.; Gan, H.; Smith, B.D. Photochem. Photobiold. Sci. 2015, 14, 1271-1281.
- "Library Synthesis, Screening and Discovery of Modified Zn(II)-bis(dipicolyamine) Probe for Enhanced Molecular Imaging of Cell Death" Plaunt, A.P.; Harmatys, K.M.; Wolter, W.R.; Suckow, M.A.; Smith, B.D. Bioconj. Chem. 2014, 25, 724-733.
- "Pre-Assembly of Near-Infrared Fluorescent Multivalent Molecular Probes for Biological Imaging" Peck, E.M.; Battles, P.M.; Rice, D.R.; Roland, F.M.; Norquest, K.A.; Smith, B.D. Bioconj. Chem. 2016, 27, 1400-1410.