The Mechanism of Action of SAAP-148 Antimicrobial Peptide as Studied with NMR and Molecular Dynamics Simulations.
NMR
antimicrobial
biomembranes
membrane topology
molecular dynamics
paramagnetic relaxation enhancement
peptides
solid-state NMR spectroscopy
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
24 Feb 2023
24 Feb 2023
Historique:
received:
28
01
2023
revised:
18
02
2023
accepted:
21
02
2023
medline:
30
3
2023
entrez:
29
3
2023
pubmed:
30
3
2023
Statut:
epublish
Résumé
SAAP-148 is an antimicrobial peptide derived from LL-37. It exhibits excellent activity against drug-resistant bacteria and biofilms while resisting degradation in physiological conditions. Despite its optimal pharmacological properties, its mechanism of action at the molecular level has not been explored. The structural properties of SAAP-148 and its interaction with phospholipid membranes mimicking mammalian and bacterial cells were studied using liquid and solid-state NMR spectroscopy as well as molecular dynamics simulations. SAAP-148 is partially structured in solution and stabilizes its helical conformation when interacting with DPC micelles. The orientation of the helix within the micelles was defined by paramagnetic relaxation enhancements and found similar to that obtained using solid-state NMR, where the tilt and pitch angles were determined based on SAAP-148 stabilizes its helical fold onto bacterial-like membranes, placing its helix axis almost perpendicular to the surface normal, thus probably acting by a carpet-like mechanism on the bacterial membrane rather than forming well-defined pores.
Sections du résumé
BACKGROUND
BACKGROUND
SAAP-148 is an antimicrobial peptide derived from LL-37. It exhibits excellent activity against drug-resistant bacteria and biofilms while resisting degradation in physiological conditions. Despite its optimal pharmacological properties, its mechanism of action at the molecular level has not been explored.
METHODS
METHODS
The structural properties of SAAP-148 and its interaction with phospholipid membranes mimicking mammalian and bacterial cells were studied using liquid and solid-state NMR spectroscopy as well as molecular dynamics simulations.
RESULTS
RESULTS
SAAP-148 is partially structured in solution and stabilizes its helical conformation when interacting with DPC micelles. The orientation of the helix within the micelles was defined by paramagnetic relaxation enhancements and found similar to that obtained using solid-state NMR, where the tilt and pitch angles were determined based on
CONCLUSIONS
CONCLUSIONS
SAAP-148 stabilizes its helical fold onto bacterial-like membranes, placing its helix axis almost perpendicular to the surface normal, thus probably acting by a carpet-like mechanism on the bacterial membrane rather than forming well-defined pores.
Identifiants
pubmed: 36986623
pii: pharmaceutics15030761
doi: 10.3390/pharmaceutics15030761
pmc: PMC10051583
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Agence Nationale de la Recherche
ID : NATURAL-ARSENAL
Organisme : Federal Ministry of Education and Research
ID : NATURAL-ARSENAL
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