Efficient Synergistic Cooperation of an Arginine-Rich Peptide and Copper Ions in Sodium Urate Crystallization Inhibition

Although many studies have focused on the role of individual biomolecules or metal ions in the crystallization behavior of sodium urate, the regulatory effects of multiple molecular species still remain mysterious. The synergistic cooperation of biomolecules and metal ions may contribute to unprecedented regulatory effects. Here, the cooperative effect of arginine-rich peptides (APs) and copper ions on the phase behavior, crystallization kinetics, and size/morphology of urate crystals was first investigated. Compared with the individual copper ion and AP, the nucleation induction time of sodium urate is prolonged dramatically (about 48 h), and the nucleation rate of sodium urate is reduced efficiently in a saturated solution due to the synergistic effect of Cu2+ and AP in stabilizing amorphous sodium urate (ASU). The length of sodium urate monohydrate crystals decreases obviously under the synergistic effect of Cu2+ and AP. The comparative experiments of common transition metal cations show that only copper ions can cooperate with AP, which may be due to the strong coordination effect between copper ions with urate and AP. Further studies show that the synergistic effect of copper ions and APs with different chain lengths on the crystallization behavior of sodium urate is significantly different. Both the guanidine functional groups and the length of peptide chains simultaneously determine the synergistic inhibition effect of polypeptides and Cu2+. This work highlights the synergistic inhibition effect of metal ions and cationic peptides on the crystallization of sodium urate, which enriches the understanding of the regulating mechanism of biological mineral crystallization using the synergy of multispecies and offers a new strategy for designing efficient inhibitors for sodium urate crystallization in gout stone diseases.