Determining the selectivity of a tetra-phosphorylated biomimetic peptide towards uranium in the presence of competing cations through the simultaneous coupling of HILIC to ESI-MS and ICP-MS

A cyclic tetra-phosphorylated biomimetic peptide (pS1368) has been proposed as a promising starting structure to design a decorporating agent of uranyl (UO₂²⁺) due to its affinity being similar to that of osteopontin (OPN), a target UO₂²⁺ protein in vivo. The determination of this peptide's selectivity towards UO₂²⁺ in the presence of competing endogenous elements is also crucial to validate this hypothesis. In this context, the selectivity of pS1368 towards UO₂²⁺ in the presence of Ca²⁺, Cu²⁺ and Zn²⁺ was determined by applying the simultaneous coupling of hydrophilic interaction chromatography (HILIC) to electrospray ionization (ESI-MS) and inductively coupled plasma (ICP-MS) mass spectrometry. Sr²⁺ was used as Ca²⁺ simulant, providing less challenging ICP-MS measurements. The separation of the complexes by HILIC was first set up. The selectivity of pS1368 towards UO₂²⁺ was determined in the presence of Sr²⁺, by adding several proportions of the latter to UO₂(pS1368). UO₂²⁺ was not displaced from UO₂(pS1368) even in the presence of a ten-fold excess of Sr²⁺. The same approach has been undertaken to demonstrate the selectivity of pS1368 towards UO₂²⁺ in the presence of Cu²⁺, Zn²⁺ and Sr²⁺ as competing endogenous cations. Hence, we showed that pS1368 was selective towards UO₂²⁺ in the presence of Sr²⁺, but also in the presence of Cu²⁺ and Zn²⁺. This study highlights the performance of HILIC-ESI-MS/ICP-MS simultaneous coupling to assess the potential of molecules as decorporating agents of UO₂²⁺.