Abstract
The n → π＊ interactions have been suggested to play a critical role in stabilizing a PPII helix, and stereoelectronic effects can have a substantial impact on polyproline conformation. Thus, understanding of the basis of polyproline structures will be one aim in this proposal. Polyproline can form either type I (PPI) or type II (PPII) helices. Besides polyproline structure, stereoelectronic effects were found to be capable of tuning protein stability. However, no study of stereoelectronic effects on β-hairpin has been reported. We choose a small β-hairpin peptide (HP7) as our model to study stereoelectronic effects on β-hairpin structure. In this work we have prepared a series of proline derivatives with an electron-withdrawing substituent on proline C4 position, such as –OH, -F and –OCH3 group. We have prepared a series of host-guest peptide, (Pro)5-X-(Pro)5-Gly-Tyr, where X = proline, and proline derivatives to evaluate the stereoelectronic effects on the transition energy barrier of the conversion between PPI and PPII conformation. Time-dependent dichroism (CD) spectra have been used to measure the conversion rates. The results show that stereroelectronic effects have a significantly impact on the conversion rates from PPII to PPI. We have also incorporated those proline derivatives with an electron-withdrawing substituent on C4 position into the HP7 peptide to investigate stereoelectronic effects on β-hairpin. The data showed that Cγ-ring puker of proline does not significantly contribute to the β-hairpin structure stability. Other forces, such as steric repulsion, cation-π and proline-aromatic interactions, need to be considered in stabilizing the β-hairpin structure.