Stabilization of Coiled-Coil Peptide Domains by Introduction of Trifluoroleucine
2001; American Chemical Society; Volume: 40; Issue: 9 Linguagem: Inglês
10.1021/bi0022588
ISSN1943-295X
AutoresYi Tang, Giovanna Ghirlanda, Nagarajan Vaidehi, Jeremy Kua, Daniel T. Mainz, William A. Goddard, William F. DeGrado, David A. Tirrell,
Tópico(s)Glycosylation and Glycoproteins Research
ResumoSubstitution of leucine residues by 5,5,5-trifluoroleucine at the d-positions of the leucine zipper peptide GCN4-p1d increases the thermal stability of the coiled-coil structure. The midpoint thermal unfolding temperature of the fluorinated peptide is elevated by 13 °C at 30 μM peptide concentration. The modified peptide is more resistant to chaotropic denaturants, and the free energy of folding of the fluorinated peptide is 0.5−1.2 kcal/mol larger than that of the hydrogenated form. A similarly fluorinated form of the DNA-binding peptide GCN4-bZip binds to target DNA sequences with affinity and specificity identical to those of the hydrogenated form, while demonstrating enhanced thermal stability. Molecular dynamics simulation on the fluorinated GCN4-p1d peptide using the Surface Generalized Born implicit solvation model revealed that the coiled-coil binding energy is 55% more favorable upon fluorination. These results suggest that fluorination of hydrophobic substructures in peptides and proteins may provide new means of increasing protein stability, enhancing protein assembly, and strengthening receptor−ligand interactions.
Referência(s)