4-Azidoproline (Azp) can tune the stability of the polyproline II (P II) conformation in collagen. The azido group in the 4R and 4S configurations stabilizes and destabilizes the PII conformation, respectively. To obtain insights into the dependence of the conformational stability on the azido configuration, we carried out Fourier transform (FT) IR experiments with four 4-azidoproline derivatives, Ac-(4R/S)-Azp-(NH/O)Me. We found that the amide I and azido IR spectra are different depending on the azido configuration and C-terminal structure. The origin of such spectral differences between 4R and 4S configurations and between C-terminal methylamide and ester ends was elucidated by quantum chemistry calculations in combination with 1H NMR and time- and frequency-resolved IR pump-probe spectroscopy. We found that the azido configurations and C-terminal structures affect intramolecular interactions, which are responsible for the ensuing conformational and thereby IR spectral differences. Consequently, 4-azidoproline conformations modulated by azido configurations can be probed by IR spectroscopy. These findings suggest that 4-azidoproline can be both a structure-control and -probing element, which enables the infrared tracking of proline roles in protein structure, function, and dynamics.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Surfaces, Coatings and Films
- Materials Chemistry