Effects of the Terminal Aromatic Residues on Polyproline Conformation: Thermodynamic and Kinetic Studies.

Abstract

In a peptide or protein, the sequence of aromatic residue-proline or proline-aromatic residue shows a high propensity in forming cis prolyl bonds due to aromatic-proline interactions. In this work, we designed and prepared the polyproline peptides with aromatic amino acids (F, Y, W) incorporated into their N-terminal or C-terminal end to investigate the effects of a terminal aromatic residue on polyproline conformation and the transition kinetics of polyproline I (PPI) to polyproline II (PPII) helices. Circular dichroism measurements reveal that the N-terminal aromatic-proline interaction imposes a more pronounced consequence on the forming propensity of PPI conformation than does the C-terminal aromatic-proline interaction in n-propanol. The propensity of forming PPI is correlated with the strength of aromatic-proline interactions in the order of Tyr-Pro > Trp-Pro > Phe-Pro. In aqueous solution, kinetic studies indicate that aromatic-substitution effects are nondirectional and indistinct on the PPI → PPII conversion rates, suggesting that aromatic-proline interactions may not be an important factor in this process. In addition, the temperature-dependent kinetics shows that the hydrophobicity of aromatic side chain may play a critical role affecting the activation enthalpy and entropy of the conversion of PPI to PPII, providing new insights into the folding of polyproline helices.