Design of New Bio-Materials: Fluorous Peptides and Metal-Peptides Frameworks.

Abstract

Perfluorocarbons have unique and valuable physical properties not found in Nature. By incorporating fluorine into proteins, it might be possible to produce biological molecules with novel and useful properties. Fluorocarbons are intrinsically more hydrophobic than hydrocarbons, and because partitioning of hydrophobic residues out of the aqueous phase is a major driving force in protein folding, are expected to be more stable. This research has focused on the perfluorinated amino acid L-5,5,5,5’,5’,5’-hexafluoroleucine (hFLeu), which has been incorporated into de novo designed peptides. A detailed investigation has been undertaken into the effect on structure and stability of systematically repacking the hydrophobic core of a model protein with hFLeu. The starting point was a 27-residue peptide, a4-H, that adopts an antiparallel 4-a-helix bundle structure, and in which the hydrophobic core comprise six layers of leucine residues introduced at the "a" and "d" positions of the canonical heptad repeat. A series of peptides were synthesized in which the central two (a4-F2), four (a4-F4), or all six layers (a4-F6) of the core were substituted hFLeu. The free energy of unfolding increases proportionally by ~0.3 (kcal/mol)/hFLeu on repacking the hydrophobic layers, so that a4-F6 is ~35% more stable than the nonfluorinated protein a4-H. One-dimensional proton, two-dimensional 1H-15N HSQC, and 19F NMR spectroscopies were used to examine the effect of fluorination on the conformational dynamics of the peptide.

Metal-peptide complexes have been synthesized from small peptide building blocks and cadmium ions resulting in some novel extended crystalline molecules. Metal-peptide complexes are of interest due to their potential applications for drug delivery, organic and biomimetic catalysts, ionic channels, chiral separating materials, food additives, and pharmaceutical purposes. Six cadmium complexes were crystallized using the di-peptides L-ala-L-ala, L-ala-L-thr, L-pro-L-ala, and L-pro-L-leu, or the tri-peptides gly-gly-gly and L-ala-L-ala-L-ala as organic linkers that form either one-dimensional or two-dimensional extended networks. The crystal structures of these may provide some “rules” for forming networks based on hydrogen bonding and hydrophobic interactions