Solution Structure of a Photo-Switchable Insect Kinin Thioxo-Analog

The photo-switchable insect kinin thioxo-analog Phe1-Tyr2-ψ[CS-N]-Pro3-Trp4-Gly5-NH2 (ψ[CS-N]2-Kinin) can change from ground state to photo-stationary state by following a pulse of UV irradiation and its bioactivity increases simultaneously. To investigate the conformation-activity relationship, the solution structure of its ground state was determined by two-dimensional NMR spectroscopy. In contrast, the photo-stationary state could not be determined because of its relatively fast thermal reisomerization. The molecular dynamics-calculated structures based on NMR constraints demonstrate that the trans Pro conformer is the predominant conformation for the ground state in aqueous solution, which was also confirmed by the very weak signal of the cis Pro conformer in the spectroscopy. The aromatic side chains of residues 2 and 4 form an electrostatic interaction rather than 1 and 4. The results explain the low bioactivity before UV irradiation, and indicate the importance of the 1-4 electrostatic interaction for the activity of insect kinins.