Biomimetic Polymerization of Tellurocysteine: Breaking the Natural Amino Acid Radioprotection Limitation.

Radioprotection remains a critical challenge in biomedicine and space exploration. As the fundamental building blocks of organisms, amino acids are gaining momentum in chemical design for in vivo radioprotection, yet their low atomic number (Z) and rapid metabolism restrict practical applications. This study addresses these limitations through the melanin-inspired polymerization of the higher Z-tellurocysteine. Motivated by the superior catalytic activity and higher Z of tellurium over selenium in both enzyme mimics and microbial systems, we hypothesized that tellurium-containing amino acid polymers could demonstrate enhanced photon interaction and radical scavenging. The exceptional nucleophilic substitution capability of tellurocysteine, which arises from its soft polarizable character, drives its bisubstitution with o-benzoquinone. The heteroatom enrichment and high-Z effect make the novel materials far exceed natural amino acid polymers in radiation shielding. The melanin-mimetic polymeric structure demonstrates enhanced radiation stability and broad-spectrum free radical scavenging ability. Following oral administration, the tellurocysteine-based polymers achieve prolonged intestinal retention, mitigating radiation-induced intestinal injury. Our work establishes a new paradigm in amino acid engineering, demonstrating how strategic non-metallic heavy atom incorporation can transform biological molecules into advanced radioprotective materials. This approach opens possibilities for developing next-generation, amino acid-derived agents with tailored pharmacokinetics and multifunctional activity.