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Chemistry

Vincent Conticello
Rational Design of Functional Nanostructures via Self-Assembly of Helical Peptides

Vincent P. Conticello, Ph.D.
(Paper was presented at the Fourth International Multi-Disciplinary Workshop on Self-assembly of Peptides and Proteins in Biology, Medicine, & Engineering” that was held from June 25-28, 2005 in Crete, Greece.

One of the most promising approaches to the fabrication of multi-functional nano-scale devices involves the self-assembly of molecular components to form ordered arrays on the nanometer to micrometer length scale. However, a critical challenge to this process lies in the rational design of synthetic materials that can self-assemble into structurally defined supramolecular aggregates that are capable of functioning as the components of these devices. In contrast, biological macromolecules routinely operate within the nano-scale size regime to create the complex supramolecular machinery that performs the chemical, electrical, and mechanical functions associated with cellular metabolism, communication, and differentiation. These complex biological machines arise from self-assembly on the basis of structural features programmed into polypeptide and polynucleotide sequences at the molecular level. As a consequence of the near-absolute control of macromolecular architecture that results from such sequence specificity, biological structural platforms may have advantages for the creation of well-defined supramolecular assemblies in comparison to synthetic polymers. Thus, the conceptual design of synthetic nano-scale devices can derive significant information from structural investigations of biologically derived supramolecular assemblies and, conversely, biological structural motifs present an attractive target for the synthesis of artificial nano-scale systems on the basis of relationships between sequence and supramolecular structure that have been established for native biological assemblies. One can envision that the structural principles implicit in biological systems can be employed for the design and construction of non-native, nano-scale materials that display the structural specificity and the chemically and spatially unique functional group presentation of native biomolecular assemblies. We describe a model for the construction of nano-scale scaffolds derived from -helical structural motifs and demonstrate that synthetic oligopeptides can be designed that self-assemble into macroscopic fibrils as a consequence of structural features programmed into its sequence at the molecular level using the criteria of this model.

Reference: Zimenkov Y, Guo L, Thiyagarajan P, Conticello VP. Rational design of a nanoscale helical scaffold derived from self-assembly of a dimeric coiled coil motif. Tetrahedron 2004, 60, 7237-7264.

Frank McDonald
Biomimetic synthesis of oxepanol terpenoid natural products

Frank E. McDonald, Rongbiao Tong, and Jason C. Valentine
Department of Chemistry, Emory University, Atlanta, Georgia 30322 USA

Introduction
Abudinol B (1, Figure 1) is a triterpenoid natural product isolated from the Red Sea sponge Ptilocaulis spiculifer, which was characterized in part by the ozonolysis products nakorone (2, also observed as a natural product) and a bicyclic keto-oxepanol 3.

Results and discussion
We recently accomplished the biomimetic tandem cyclization of diepoxide 6 bearing a propargylic silane substituent to give tricyclic allene 7 (80% yield), which was converted into ent-nakorone. The analogous cyclization of diepoxide 8 bearing enol silyl ether provided a bicyclic ketone 9 (50% yield), corresponding to the enantiomer of abudinol B ozo-nolysis product 3.

Conclusions
Having completed short biomimetic syntheses of polycyclic ketones 2 and 3, we are currently explor-ing extensions of this approach to the total synthesis of abudinol B.