2024/12/20 by David Silva-Brea, Julen Aduriz‐Arrizabalaga, David De Sancho +1 · 1 voice
Medicine · Chemistry · Biochemistry, Genetics and Molecular Biology · #Metal complexes synthesis and properties #Molecular Sensors and Ion Detection #DNA and Nucleic Acid Chemistry
paper · doi:10.1016/j.jinorgbio.2024.112807
openalex publication_date 2024/12/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Mimosine, a non-essential amino acid derived from plants, has a strong affinity for binding divalent and trivalent metal cations, including Zn 2+ , Ni 2+ , Fe 2+/3+ , and Al 3+ . This ability endows mimosine with significant antimicrobial and anti-cancer properties, making it a promising candidate for therapeutic applications. Previous research has demonstrated the effectiveness of mimosine-containing peptides as metal chelators, offering a safer alternative to conventional chelation agents. However, optimizing the design of these peptides necessitates a thorough understanding of their conformational ensembles in both free and metal-bound states. Here, we perform an in-depth analysis of mimosine-containing peptides using long-time MD simulations and quantum calculations to identify key factors critical for peptide design. Our results show that these peptides can achieve metal-binding affinities comparable to established aluminum chelators like deferiprone and citrate. Additionally, we underscore the crucial role of the peptide backbone in reducing the entropic penalty associated with metal binding. We propose strategies to modulate this entropic penalty—a challenging thermodynamic property to evaluate but essential in complexes between short peptides and metals—by incorporating proline residues and optimizing sequence length. These approaches offer promising pathways for developing efficient peptide chelators. • Mimosine-containing peptides are a promising new family of metal chelators, according to quantum mechanical calculations. • Entropic effects, derived from Molecular Dynamics simulations, are important thermodynamic modulators of the metal binding affinity. • Changes in peptide sequence and length can be used as factors to reduce the entropic penalty upon metal binding.