A low-toxicity uranyl-selective-binding linear pentapeptide sequence as a potential uranium decorporation agent.

Area of Science:

• Biochemistry
• Toxicology
• Materials Science

Background:

• Uranium contamination requires effective and safe chelating agents for *in vivo* removal.
• Amino acid-based peptides offer low toxicity and potential for actinide chelation.
• Developing selective chelators is crucial for minimizing off-target effects.

Purpose of the Study:

• To design and evaluate a novel phosphorylated peptide, PP-B, as a selective chelating agent for uranyl ions (*in vivo*).
• To assess the affinity, selectivity, and decorporation efficiency of PP-B compared to existing treatments.

Main Methods:

• Rational design of a short phosphorylated peptide sequence (PP-B).
• Determination of the association constant for the peptide-uranyl complex.
• Density Functional Theory (DFT) calculations to understand binding interactions.
• *In vivo* uranyl decorporation assays.

Main Results:

• PP-B demonstrated high affinity and selectivity for uranyl (UO₂²⁺) over other essential trace elements.
• The association constant for the PP-B-uranyl complex was determined to be 7.3 × 10⁵ M^-1.
• DFT calculations indicated strong binding between the peptide's phosphate group and the uranyl center.
• *In vivo* studies showed PP-B significantly outperformed DTPA in uranyl decorporation efficiency and exhibited lower toxicity.

Conclusions:

• PP-B is a highly selective and efficient chelating agent for uranyl ions.
• The peptide's strong affinity is attributed to the phosphate group's interaction with the uranyl center.
• PP-B represents a promising novel therapeutic candidate for uranium decorporation with improved safety and efficacy over DTPA.