This research program aims to develop and test electronic principles governing electron transfer processes in biomolecules by the design, synthesis, and time-resolved laser kinetic characterization of electronically active model peptides. The foundation of the experimental strategy, established during the NIH FIRST grant, is the de novo design of special peptides rich in the uniquely helix-promoting residue alpha-amino- isobutyric acid (Aib). Peptides with 75% Aib composition form highly well- defined 3-10 helices, as verified directly in solution by 2D NMR. These conformationally stable helices serve as hosts enabling the incorporation of electronically active residues at sequence positions selectable at will. With these systematically varied sequences the principles by which molecular structure controls non-local electronic interactions can be mapped. The key components of this """"""""Molecular Optical Rail"""""""" strategy are pairs of novel aromatic redox amino acids. These special redox amino acids feature conformationally locked side-chains. Transient absorption studies have begun to delve into the intrahelical electron transfer as a function of sequence and the nature of intervening amino acids. This direct measurement of electron transfer acceleration or retardation by natural (non-redox) amino acids is of considerable and timely importance. An entirely new investigation of the Aib-rich hydrophobic sequences as model peptides for isolated membrane-penetrating helices is also proposed. Aib peptides bearing zwitterionic polar head groups will be synthesized and their interaction with lipid bilayers will be studied by fluorescence techniques to assess key principles for the ultimate de novo design of helical membrane proteins. Membrane-buried electron transfer energetics and kinetics at the peptide level will then be established with a new membrane biophysical technique, """"""""supported lipid monolayer bioelectrochemistry"""""""" on alkylated gold electrodes.
