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.
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