475d DNA-Encapsulation Using Self-Assembled Peptide Architectures

Raymond Tu, Department of Chemical Engineering, City College of City University of New York, 140th St. at Convent Ave. T344, New York, NY 10031

In nature, counterion-mediated DNA-condensation is the basis for control of translational mechanisms, and the development of biotechnologies that mimic this phenomenon can be applied to gene encapsulation and DNA-separation. Biologically inspired molecules with the capacity to self-assemble and distribute charge in a spatially controlled fashion offer a versatile tool for examining the complex behavior. We investigate the cooperative process of DNA-condensation with a set of rationally designed peptide building blocks, where the construction and application of such ‘bottom-up' assemblies is described in three parts:

1. Predictive folding algorithms – Applying chemical periodicity within the sequence relevant to the target secondary structure, a-helix (3.5 residues/turn) or b-sheet (alternating residues), gives spatial control of charged and hydrophobic regions

2. Precision synthesis - FMOC-solid phase peptide techniques provide a well-developed route for the synthesis of monodispersed peptides, where multivalent cationic non-natural amino-acids can be included to increase the local charge density.

3. Characterization of self-assembly and binding - Duplexing of such techniques as circular dichroism spectroscopy and Förster resonance energy transfer will allow the concurrent detection of secondary structure and DNA-condensation.

These sequences that hybridize structure-nucleating and ligand-binding components within self-assembling peptide building blocks result in control over spatial, chemical and physical properties. This allows us to investigate the interaction energetics and the influence of cooperative structure formation associated with DNA-peptide complexation behavior.



Web Page: www2.ccny.cuny.edu/prospective/engineering/departments/chemical/faculty/Faculty-Professor-TU.cfm