Designing mimosine-containing peptides as efficient metal chelators: Insights from molecular dynamics and quantum calculations.

Autor: Silva-Brea D; Faculty of Chemistry (UPV/EHU), Manuel Lardizabal 3, Donostia-San Sebastian 20018, Spain; DIPC, Manuel Lardizabal 4, Donostia-San Sebastian 20018, Spain., Aduriz-Arrizabalaga J; Faculty of Chemistry (UPV/EHU), Manuel Lardizabal 3, Donostia-San Sebastian 20018, Spain; DIPC, Manuel Lardizabal 4, Donostia-San Sebastian 20018, Spain., De Sancho D; Faculty of Chemistry (UPV/EHU), Manuel Lardizabal 3, Donostia-San Sebastian 20018, Spain; DIPC, Manuel Lardizabal 4, Donostia-San Sebastian 20018, Spain. Electronic address: david.desancho@ehu.eus., Lopez X; Faculty of Chemistry (UPV/EHU), Manuel Lardizabal 3, Donostia-San Sebastian 20018, Spain; DIPC, Manuel Lardizabal 4, Donostia-San Sebastian 20018, Spain. Electronic address: xabier.lopez@ehu.eus.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2024 Dec 20; Vol. 264, pp. 112807. Date of Electronic Publication: 2024 Dec 20.
DOI: 10.1016/j.jinorgbio.2024.112807
Abstrakt: 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.
Competing Interests: Declaration of competing interest There are no conflicts to declare.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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