News and Publications

Molecular Assemblies, Materials, and Chemical Networks

M.R. Ghadiri, D.T.Y. Bong, K. Broo, M.J. Churchill, T.D. Clark, J.D. Hartgerink, M.P. Isler, A. Janshoff, A.J. Kennan, H.S. Kim, K. Krähenbühl, K. Kumar, V.S.-Y. Lin, K. Motesharei, J. Quesada-Sanchez, A. Saghatelian, C. Steinem, M. Vollmer, Y. Yokobayashi

Our group is involved in a multidisciplinary research program that seeks to uncover new avenues in the design and construction of functionally predetermined molecular and supramolecular assemblies such as peptide nanotubes, synthetic enzymes, replicators, biomaterials and composites, and nonlinear chemical networks. Our approach is to bring about deliberate self-organizing, self-assembling, and self-replicating processes by exploiting the molecular information stored within the covalent structure of a given design and the readout and processing of this information through noncovalent chemical reactions.

PEPTIDE NANOTUBES

Open-ended hollow tubular structures with nanometer dimensions, termed "peptide nanotubes," are a new class of functional biomaterials (Fig. 1). These species, which are constructed by stacking appropriately designed cyclic peptide subunits, have novel applications in biological and materials sciences. For example, cyclic peptides have been designed to self-assemble inside lipid membranes to form transmembrane channels and pore structures that can effectively mimic the transport action of biological counterparts. Such membrane-active tubular assemblies have antimicrobial and cytotoxic activities and are expected to be useful as novel chemotherapeutics and drug-delivery vehicles. Self-assembling peptide nanotubes are also efficacious as novel materials, especially in the fabrication of transition-metal nanocomposites and in the design of solid-state biosensors.

DE NOVO DESIGN OF SYNTHETIC CATALYSTS

Preparation of synthetic molecules that have the remarkable efficiencies characteristic of natural biopolymer catalysts remains a formidable challenge for chemical biology. Despite advances in the understanding of protein structure and function, efforts to produce wholly synthetic catalytic peptides have typically resulted in compounds with questionable structural stability and reactivity. Recently, we described synthetic peptides, based on the coiled-coil structural motif, that catalyze peptide fragment condensation reactions in a highly sequence-specific and diastereoselective manner with catalytic efficiencies in excess of 10⁵. We also successfully applied the basic principles used in the design of peptide ligases to construct peptide replicators and nonlinear chemical networks. Current efforts are focused on the rational design of hydrolases and the construction of catalysts with more complex active sites.

Other ongoing research activities in our laboratory include the study of early protein folding kinetics, design of nanocomposites and photoswitchable thin films, heterogeneous catalysts, and fabrication of solid-state biosensors.

PUBLICATIONS

Case, M.A., Ghadiri, M.R., Mutz, M.W., McLendon, G.L. Stereoselection in designed three-helix bundle metalloproteins. Chirality 10:35, 1998.

Clark, T.D., Buehler, L.K., Ghadiri, M.R. Cyclic ß-peptide nanotubes as artificial transmembrane ion channels. J. Am. Chem. Soc. 120:651, 1998.

Kim, H.S., Hartgerink, JD., Ghadiri, M.R. Oriented self-assembly of cyclic peptide nanotubes in lipid membranes. J. Am. Chem. Soc. 120:4417, 1998.

Lee, D.H., Severin, K., Ghadiri, M.R. Autocatalytic networks: The transition from molecular self-replication to ecosystems. Curr. Opin. Chem. Biol. 1:491, 1997.

Lee, D.H., Severin, K., Yokobayashi, Y., Ghadiri, M.R. Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390:591, 1997.

Severin, K., Lee, D.H., Martinez, J.A., Vieth, M., Ghadiri, M.R. Dynamic error-correction in autocatalytic peptide networks. Angew. Chem. Int. Ed. 37:126, 1997.