Capturing an elusive but critical element: Natural protein enables actinium chemistry

Abstract

Demystifying the elusive chemistry of actinium leads to novel opportunities in radioisotope production and nuclear medicine.

Engineering lanmodulin's selectivity for actinides over lanthanides by controlling solvent coordination and second-sphere interactions

“…Such a partner might be the outer membrane receptor in the lanM gene cluster, if the hypothesis that LanM is a secreted macromolecular lanthanophore/actinophore 55 – to complement a separate small-molecule system recently described in a pre-print 86 – is correct. Our observation also accounts for LanM's complexes with Ac 3+ and La 3+ being the most resistant to chelators that would be encountered in Nature like citrate, 7 carbonate, and phosphate, 54 despite having lower affinity 55 than Nd 3+ , Am 3+ , and Cm 3+ – an unusual property that can be exploited for separations.…”

Lanmodulin peptides – unravelling the binding of the EF-Hand loop sequences stripped from the structural corset

“…22 In addition, it was recently shown that LanM has a high affinity not only for Lns, but also for actinides (Ans). [25][26][27] Interestingly, all conducted studies observe a higher affinity of LanM for the Ans than for the Lns. [25][26][27] Due to the aforementioned similarities between calcium and Lns, calcium-binding proteins such as calmodulin (CaM) have been used in the past as template for specific Ln-binding peptides.…”

“…[25][26][27] Interestingly, all conducted studies observe a higher affinity of LanM for the Ans than for the Lns. [25][26][27] Due to the aforementioned similarities between calcium and Lns, calcium-binding proteins such as calmodulin (CaM) have been used in the past as template for specific Ln-binding peptides. [28][29][30][31] Particularly noteworthy are lanthanide-binding tags (LBTs), which have been developed starting from EF-Hand binding loop sequences as a tool for analysing protein structures and protein-protein interactions by incorporating those short Ln-binding amino acid sequences (the LBTs) into the protein structure, which enables analysis via methods involving luminescence, NMR spectroscopy and others.…”

“…[38][39][40] LanM, a protein, designed by nature to bind Lns with a high affinity for Ans, is an attractive target for the development of REE-recycling and Ans-separation methods. 24,26,27,41,42 With LanM as inspiration, de novo proteins, 43 peptides 44 and organic ligands can be envisioned. An example of such a bioinspired approach is the use of pyrroloquinoline quinone (PQQ; the cofactor of the aforementioned Ln-MDHs) in the separation of Lns by precipitation in aqueous solution.…”

Americium preferred: lanmodulin, a natural lanthanide-binding protein favors an actinide over lanthanides

“… 20 During the preparation of this manuscript, a preprint stated that LanM is able to bind actinium with a higher affinity compared to, for example, the REE yttrium. 21 Previously, an NMR structure of LanM with Y 3+ has been reported, and during the review process of this manuscript a study demonstrating binding of Am and Cm to LanM, was published. 19,22 Here, we evaluate the potential of LanM to bind the An neptunium, plutonium, americium and curium and compare the relative binding affinity § § Here we use the term relative binding affinity, because absolute values cannot be obtained from the competition experiment performed.…”