Design of reversible hydrogels

o Substitution of leucine residues by 5,5,5-trifluoroleucine at the d-positions of the leucine zipper peptide GCN4-p1 increases the thermal stability of the coiled-coil structure. The modified peptide is more resistant to chaotropic denaturants while maintaining the same dimeric aggregation order, and the free energy of folding of the fluorinated peptide is elevated by 50% compared to the hydrogenated form. In collaboration with David Tirrell's group at Caltech we have calculated the free energy of dimerization of the gnc4 native zipper and the trifluoro and the hexafluoro leucine gcn4. The calculations distinguish the different stereoisomers of trifluoroleucine zippers as shown in the figure below. These results suggest that fluorination of peptide and protein hydrophobic cores may provide a new means of increasing protein stability, enhancing protein assembly and strengthening receptor-ligand interactions. The calculated increase in the stability(55%) is the very close to the experimentally measured increase in stability (57%) due to fluorination.