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 (UO 2 2+ ) due to its affinity being similar to that of osteopontin (OPN), a target UO 2 2+ protein in vivo. The determination of this peptide's selectivity towards UO 2 2+ in the presence of competing endogenous elements is also crucial to validate this hypothesis. In this context, the selectivity of pS1368 towards UO 2 2+ in the presence of Ca 2+ , Cu 2+ and Zn 2+ 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. Sr 2+ was used as Ca 2+ simulant, providing less challenging ICP-MS measurements. The separation of the complexes by HILIC was first set up. The selectivity of pS1368 towards UO 2 2+ was determined in the presence of Sr 2+ , by adding several proportions of the latter to UO 2 (pS1368). UO 2 2+ was not displaced from UO 2 (pS1368) even in the presence of a ten-fold excess of Sr 2+ . The same approach has been undertaken to demonstrate the selectivity of pS1368 towards UO 2 2+ in the presence of Cu 2+ , Zn 2+ and Sr 2+ as competing endogenous cations. Hence, we showed that pS1368 was selective towards UO 2 2+ in the presence of Sr 2+ , but also in the presence of Cu 2+ and Zn 2+ . This study highlights the performance of HILIC-ESI-MS/ICP-MS simultaneous coupling to assess the potential of molecules as decorporating agents of UO 2 2+ .