Hydrophobic core formation and secondary structure elements in uranyl(VI)-binding peptides

Area of Science:

• Biochemistry
• Supramolecular Chemistry
• Materials Science

Background:

• Uranyl(VI) is a toxic heavy metal ion requiring effective sequestration strategies.
• Designing high-affinity ligands for selective uranyl(VI) capture remains a significant challenge.
• Peptide-based designs offer tunable properties for metal ion binding.

Purpose of the Study:

• To develop novel cyclic peptides and modified calmodulin EF-hand motifs for high-affinity uranyl(VI) binding.
• To investigate the mechanisms underlying selective uranyl(VI) recognition and binding.
• To explore the potential of these designs for uranyl(VI) remediation or sensing applications.

Main Methods:

• De novo design of cyclic peptides with specific binding pockets.
• Engineering of a modified EF-hand motif based on calmodulin.
• Computational modeling and experimental validation of uranyl(VI) binding affinity and selectivity.
• Characterization of the structural features of uranyl(VI)-bound peptides.

Main Results:

• Newly designed cyclic peptides exhibit high affinity for uranyl(VI) through backbone coordination.
• Engineered EF-hand motifs demonstrate strong uranyl(VI) binding via electrostatic interactions with negatively charged side chains.
• Acidic conditions enhance the selectivity of cyclic peptides for uranyl(VI).
• Formation of secondary structures and hydrophobic cores is crucial for high-affinity binding in the EF-hand motif.

Conclusions:

• Both cyclic peptides and modified EF-hand motifs represent promising scaffolds for uranyl(VI) capture.
• The design strategies highlight the importance of coordination chemistry, electrostatic interactions, and structural integrity for uranyl(VI) binding.
• These engineered peptides offer potential for developing advanced materials for uranyl(VI) management.