Selective binding of UO22+ by different peptide families

Actinide interaction with proteins and peptides is little explored field in actinide chemistry, though there are biophysical studies where relative high affinity was found for U interaction with proteins. However, in vivo studies showed minor increases of U in serum, attributed to rapid urinary excretion. U–protein interaction is apparently not the major pathway associated with U genotoxicity. Nevertheless there are other scenarios where U interaction with amino acids can become potentially important such as extraction of uranium from sea water using protein (e.g. Wang et al. Angew. Chem. Int. Ed. 2019, 131, 11911). Here, we studied selective binding of UO22+ with several different peptide families including (a) cyclic peptides consisting of 6 –10 amino acids, (b) non–cyclic peptides of similar size, (c) 33–amino acid peptide corresponding to EF hand of the calcium–binding site I of calmodulin. For small peptides (a and b), we used standard DFT approaches to study their interaction with UO22+. For a larger peptide family (c), classical molecular dynamics (MD) simulations were used to study binding of peptide with UO22+, followed by fragment molecular orbital (FMO) calculations (e.g. Rossberg et al. Chem. Comm. 2019, 55, 2015) to study their interactions at a quantum chemical level. At the meeting, we will present the strategy to design peptides which have high affinity and selectivity towards UO22+. This work was partially funded by Grant-in-Aid for Scientific Research of the Japan Society for the Promotion of Science.