Crystal and molecular structure of the analgesic tetrapeptide, L-Phe-L-Leu-L-Pro-L-Ser

The tetrapeptide, L-Phe-L-Leu-L-Pro-L-Ser (FLPS), alleviates pain in a rat model of post-surgery pain. The crystal structure of the tetrapeptide is solved at high resolution (0.54 Å). The asymmetric unit contains two FLPS molecules, one Zn ion, and four molecules of water with a formula of [Zn(C23H33N4O6)2(H2O)4]. Each Zn ion is octahedrally coordinated with Phe and Ser residues from four peptide molecules [2N+4O]. The linking of Phe and Ser residues of one FLPS molecule to three other FLPS molecules by Zn ion forms a complex consisting of chains of metal ions and FLPS molecules oriented along the b axis. Analysis of molecular packing reveals the coexistence of two FLPS conformers in the same crystal. The crystallographic parameters for [Zn(C23H33N4O6)2(H2O)4] are as follows: space group P21 21 21 , a = 9.8698(2) Å, α = 90°, b = 20.1844(4) Å, β = 90°, c = 25.9302(6) Å, γ = 90°. Volume = 5165.71(19) Å(3), Z = 4, density (calc) = 1.364 Mg/cm(3), and agreement factor R1 = 4.13%.