Molecular Self-Assembly of Peptide Nanostructures: Mechanism of Association and Potential Uses

Meital      Reches; Ehud      Gazit

Abstract

Molecular self-assembly offers unique directions for the fabrication of novel supramolecular structures and advanced materials. The inspiration for the development of such structures is often derived from self-assembling modules in biology, as natural systems form complex structures from simple building blocks such as amino acids, nucleic acids and lipids. Peptide-based nanostructures indicate an important route toward the production of ordered nanostructures as several studies had demonstrated their ability to form well organized assemblies. This includes cyclic peptides designed with alternating D- and L- amino acids, amphiphile peptides, peptide-conjugates and ionic self-complementary peptides. A naturally occurring self-assembly process of nano scale objects by polypeptides is that of amyloid fibril formation. These 7-10 nm fibrillar assemblies were already used for the formation of conductive nanowires. Short peptides have been used as model systems to study the molecular mechanism that leads to amyloid fibril formation. Based on the analysis of short amyloid forming fragments, it was recently suggested by our group and others that aromatic interactions may play a significant role in the process of amyloid fibrils formation in several cases. This hypothesis led to the discovery that the core recognition motif of the Alzheimers β-amyloid polypeptide, the diphenylalanine element, has all the molecular information needed to self assemble into a novel class of peptide nanotubes. A highly similar analog and the simplest aromatic dipeptide, the diphenylglycine, forms spherical nanometric assemblies. Both designed and peptide fragment nanostructures were suggested to have many applications in various fields including molecular electronics, tissue engineering, and material science. Biography: Meital Reches received her B.Sc. in Biology from Tel Aviv University in 2002. She joined Prof. Ehud Gazit research group at the Department of Molecular Microbiology and Biotechnology already as an undergraduate student and continued her graduate studies under his guidance in 2002. Her Ph.D. thesis focuses on self assembly of short peptides into superamolecular structures. She was awarded with the Dan David Scholarship for outstanding doctoral students and the Clore Foundation Program Doctoral Scholarship. Ehud Gazit received his B.Sc. (summa cum laude) in 1991, under the framework of Tel Aviv University Special Program for Outstanding Students. His Ph.D. (with distinction) was awarded in 1997 for his thesis performed under the guidance of Prof. Yechiel Shai at the Department of Membrane Research and Biophysics, Weizmann Institute of Science. In the years 1997-2000 he performed postdoctoral research under the guidance of Prof. Robert T. Sauer at the Massachusetts Institute of Technology (MIT). Ehud Gazit joint Tel Aviv University as a faculty member in October 2000 and he is currently an Associate Professor at the Department of Molecular Microbiology and Biotechnology. Ehud Gazit also holds a visit appointment at the Center of Biomedical Engineering of MIT. During his career Ehud Gazit was awarded with several awards including the John F. Kennedy Award and the Landau Research Award.

Keywords: Molecular Recognition, Nanotubes, Nanospheres, Peptide Nanostructures, Self-Assembly, Supramolecular Biochemistry