Design of reversible hydrogels
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.