Jean A. Chmielewski

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

Assembly and disassembly of peptides and proteins is a recurring theme in the research of our group. Self assembly is an essential element in the biological activity of biopolymers. In our research we design and synthesize self assembling peptide systems with novel binding and catalytic features. Our work spans many areas of interest including:

· Covalent Stabilization of Large Helical Bundles

· Peptide-Enhanced Liposomal Drug Delivery

· Self-Replicating Peptides

Work in these areas has the promise of producing viable ways of targeting drugs to the site of their action in the body, and has the potential to answer fundamental questions on the nature of the molecular origins of life.

Many proteins also associate to form dimers and larger assemblies. The enzymes of HIV, for instance, rely on dimer formation for optimum catalytic activity. Transcription factors also form dimers, and this dimerization event is essential for their specific DNA binding properties. We have prepared unique inhibitors of dimerization in a number or areas including:

· Enzymes of HIV: Protease and Integrase

· Transcription Factors: E47, Fos/Jun, E2A-HLF, NF-kappaB

· Restriction Endonucleases

Inhibitors of this type may lead to potent classes of anti-AIDS or anti-cancer therapeutic agents, and also provide an increased understanding of the intermolecular contacts at protein subunit interfaces.

Selected Publications:

R. Zutshi, J. Franciskovich, M. Shultz, B. Schweitzer, P. Bishop, M. Wilson, J. Chmielewski, "Targeting the Dimerization Interface of HIV-1 Protease: Inhibition with Crosslinked Interfacial Peptides", J. Am. Chem. Soc., 119, 4841 (1997).

K. Vogel, S. Wang, P. Low, J. Chmielewski, "Peptide-Mediated Release of Folate-Targeted Liposome Contents from Endosomal Compartments" J. Am. Chem. Soc., 118, 1581 (1996).

S. Yao, I. Ghosh, R. Zutshi, J. Chmielewski, "Selective Amplification via Auto- and Cross-Catalysis in a Replicating Peptide System", Nature., 396, 447 (1998).