Born Syracuse, New York, 1975. S.U.N.Y. O.C.C. A.S., 1995. S.U.N.Y. College of Environmental Science and Forestry B.S., magna cum laude 1998. The University of Chicago, M.S., 2000 Ph.D., 2005. The Scripps Research Institute, Post-Doc, 2005-2007. California State University Long Beach, Assistant Professor, 2007- Awards Edith Barnard Memorial Award in Chemistry for Service to Others, The University of Chicago May 2005 Freud Departmental Citizenship Award, The University of Chicago May 2005 NIH Pre-doctoral Training Grant for Chemistry and Biology, National Institutes of Health 2000-2002 James Franck Fellowship, The University of Chicago 1999 Merck Award for Environmental Biochemistry, Merck & Co. Inc. 1998 Ernest Sondheimer Memorial Award 1998 John Meyer Environmental Chemistry Award 1997 Michael P. Schramm Assistant Professor Office: MLSC 335 Phone: (562)-985-1866 Email: schramm@csulb.edu Web: http://chemistry.csulb.edu/schramm/   News: September 2009: Jenny Pham and Michelle Hansol Park presented individual posters on their progress towards preparing a library of alpha-helical Peptidomimetics at the 2009 CNSM Poster Session. August 2009: New Publication in Tetrahedron "Translational motion insideself-assembled encapsulation complexes " Dariush Ajami, Michael P. Schramm, Julius Rebek, Jr.* Tetrahedron 65 (2009) 7208–7212. July 2009: Massiel Trujillo was selected to present at the UC Berkeley 2009 McNair Symposium about her work on the effects of Cavitand additives on Critical Micelle Concentration. May 2009: Michelle Hansol Park was awarded an Allergan Fellowship to support her work on the synthesis of a Library of alpha-helical Peptidomimectics. May 2009: Hai Hoang was awarded a Provost Student Summer Stipend to support his continued work on Selective Small Molecule Membrane Transport.   Research Interests: Molecular recognition is the study of how and why molecules interact. At its essence lies the attraction of molecules at energy levels “weaker than covalent.” Hydrogen bonding, metal coordination, and the hydrophobic effect cover some of these possible forces. In nature we find countless crucial interactions predicated on noncovalent interactions such as; enzyme-substrate recognition, DNA-protein binding, and ion-receptor transport. From a synthetic point of view these principles have strongly influenced areas of research from drug design to materials science to molecular self-assembly. Our research uses molecular recognition as a design principle to develop new synthetic molecules that are compatible with and capable of regulating biological function. Selective Small-Molecule Membrane Transport via Synthetic Molecular Receptors Recently, we discovered that a series of cavitands (synthetic vase-shaped molecular receptors) exhibited selective recognition when immersed in aqueous phosphocholine micelles. Cavitands of this type typically only function in organic solvents. In water they display very poor solubility – in fact their function as a receptor is non-existent in pure water as they tend to form cavity-less dimers. In the presence of micelles, however, their behavior as selective receptors was restored. Adamantanes served as an ideal guest “handle.” We appended this particular handle with a variety of functional groups (in the illustrated case a green fluorophore) and these guests were observed to bind on the NMR timescale. This binding event occurred despite the guest’s lack water solubility and the presence of a virtual sea of competing alkyl chains present in the micelle interior.     Micelles serve as the most simplistic model of biological membranes. In the next stage of this research program we will employ our cavitands and study whether they are capable of transporting small molecules across the lipid bilayer of unilamellar vesicles. The ultimate goal of this project is the transport of small drug-like molecules across mammalian cell membranes. Students interested in synthesis, host-guest interactions, membrane transport, or fluorescence microscopy are encouraged to inquire further. Modular α-Helical Peptidomimetics The field of peptidomimetics emerged in part due to the failure of peptides and proteins to serve as drugs. Several factors contribute to poor protein/peptide bioavailability such as: proteolytic degradation, poor membrane penetration, and conformational instability. The discovery that proteins typically interact through small portions of their total surface established a new paradigm for small molecule design; to localize amino acid side chain analogs in space such that they interact/interrupt as the progenitor protein would. The α-helix is an important structural model in the study of protein-protein interactions (e.g. calmodulin-smMLCK) and has served as a peptidomimetic model in the study of apoptosis. The Bak-Bcl and p53-HDM2 interactions involve key α-helical subdomains as their main recognition motif and serve as important regulatory mechanisms for cell death, thus making them both of great interest to chemotherapy. Several studies have already been directed at these targets, the most notable relying on a terphenyl scaffold that successfully positions the side-chain analogs in space mimicking the native protein. Molecular modeling demonstrates this, but true validation was shown through in vitro analysis, which resulted in sub-micromolar hits. The key to understanding α-helical mimetic design is that the side chains of the parent protein responsible for activity are on the same face of the helix, and are arranged at either i, i+3, and i+7, or i, i+4, and i+7 intervals. The figure below demonstrates the geometric similarities between a natural peptide made of 8 alanine residues and one of our mimetic prototypes. The key residues are in good spatial agreement as measured by molecular modeling.     Almost all peptidomimetic strategies to date suffer from several major problems: 1) limited water solubility, 2) non-modular, and 3) lengthy (10+ step) syntheses. We aim to overcome these challenges using a combinatorial approach, where a library of building blocks are assembled in a few simple steps to generate libraries of 100s to 1000s of compounds whose properties can readily be tested using in vitro high-throughput screening techniques. Students interested in synthesis, drug-design, drug-screening, or molecular modeling are encouraged to inquire further. Chirality and Catalysis The study of chirality and catalysis are two cornerstones of modern organic synthesis. We are currently exploring these areas from a less traditional angle. Students intersted in these areas are encouraged to make contact for more details.   Selected References Effects of Remote Chiral Centers on Encapsulated Molecules Schramm, M. P., Rebek, J., Jr. Accepted New J. Chem. 2008. Influence of Remote Asymmetric Centers in Reversible Encapsulation Complexes Schramm, M. P., Restorp, P., Zelder, F., Rebek, J., Jr. Accepted J. Am. Chem. Soc. 2008. Guest Recognition with Micelle-Bound Cavitands Schramm, M. P., Hooley, R. J., Rebek, J., Jr. J. Am. Chem. Soc. (Article), 2007, 129, 9773-9779. Assembly of Hybrid Synthetic Structures Ajami, D., Schramm, M. P., Volonterio, A., Rebek, J. Angew. Chem. Int. Ed. 2007, 46, 242-244. Moving Targets: Recognition of Alkyl Groups Schramm, M. P., Rebek, J. Chem. --Eur. J. (Review, Cover Article) 2006, 12, 5924-5933. Silver Catalzyed [2+2] Cycloaddtions of Siloxyalkynes Sweis, R. A., Schramm, M. P., Kozmin, S. A. J. Am. Chem. Soc. 2004, 7442-7443. Siloxyalkyne-Alkene Metathesis: Rapid Access to Highly Functionalized Enones. Schramm, M. P., Reddy, D. S., Kozmin, S. A. Angew. Chem. Int. Ed. 2001, 4274-4277.