Role of Peptide Associations in Enhancing the Antimicrobial Activity of Adepantins: Comparative Molecular Dynamics Simulations and Design Assessments DOI Open Access
Matko Maleš, Davor Juretić, Larisa Zoranić

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12009 - 12009

Опубликована: Ноя. 8, 2024

Adepantins are peptides designed to optimize antimicrobial biological activity through the choice of specific amino acid residues, resulting in helical and amphipathic structures. This paper focuses on revealing atomistic details mechanism action aligning design concepts with peptide behavior simulation results. Notably, Adepantin-1a exhibits a broad spectrum against both Gram-positive Gram-negative bacteria, while Adepantin-1 has narrow bacteria. The results showed that one main differences is extent aggregation. Both exhibit strong tendency cluster due amphipathicity embedded during process. However, more potent forms smaller aggregates than Adepantin-1, confirming idea optimal aggregations, not strongest favor activity. Additionally, we show incorporation cell penetration region affects mechanisms promotes stronger binding anionic neutral membranes.

Язык: Английский

Activity and Safety Optimization of Mesoricin: A Dual-Domain Antifungal Peptide from Mesorhizobium sp. DOI
Hongwei Zhao, Simei Sun,

Xiang Ding

и другие.

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Cryptococcus neoformans infections pose a significant global health threat. This study introduces mesoricin, novel dual-domain antimicrobial peptide (AMP) scaffold derived from Mesorhizobium sp. identified using an in silico quantitative antifungal activity index (AFI). The structure comprises α-helix domain, which disrupts microbial membranes but exhibits highly hemolytic activity, and β-sheet targets intracellular energy metabolism resilient pathways. Rational design through domain removal AFI-guided mutations yielded mesoricin variant with enhanced reduced cytotoxicity. optimized exhibited broad-spectrum against various Candida species (MIC 8-16 μg/mL) while maintaining high biosafety (IC50 > 128 μg/mL human cell lines). Particularly, the demonstrated fungicidal effects at sub-MIC levels superior biofilm control capabilities compared to prototype peptide. These findings highlight mesoricins as promising for AMP development targeting infections.

Язык: Английский

Процитировано

0
Role of Peptide Associations in Enhancing the Antimicrobial Activity of Adepantins: Comparative Molecular Dynamics Simulations and Design Assessments DOI Open Access
Matko Maleš, Davor Juretić, Larisa Zoranić

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12009 - 12009

Опубликована: Ноя. 8, 2024

Adepantins are peptides designed to optimize antimicrobial biological activity through the choice of specific amino acid residues, resulting in helical and amphipathic structures. This paper focuses on revealing atomistic details mechanism action aligning design concepts with peptide behavior simulation results. Notably, Adepantin-1a exhibits a broad spectrum against both Gram-positive Gram-negative bacteria, while Adepantin-1 has narrow bacteria. The results showed that one main differences is extent aggregation. Both exhibit strong tendency cluster due amphipathicity embedded during process. However, more potent forms smaller aggregates than Adepantin-1, confirming idea optimal aggregations, not strongest favor activity. Additionally, we show incorporation cell penetration region affects mechanisms promotes stronger binding anionic neutral membranes.

Язык: Английский

Процитировано

0