Manipulating Active Structure and Function of Cationic Antimicrobial Peptide CM15 with the Polysulfonated Drug Suramin: A Step Closer to in Vivo Complexity.
IR spectroscopy
antimicrobial peptides
circular dichroism
folding
suramin
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
14 06 2019
14 06 2019
Historique:
received:
21
12
2018
pubmed:
6
2
2019
medline:
9
4
2020
entrez:
6
2
2019
Statut:
ppublish
Résumé
Antimicrobial peptides (AMPs) kill bacteria by targeting their membranes through various mechanisms involving peptide assembly, often coupled with disorder-to-order structural transition. However, for several AMPs, similar conformational changes in cases in which small organic compounds of both endogenous and exogenous origin have induced folded peptide conformations have recently been reported. Thus, the function of AMPs and of natural host defence peptides can be significantly affected by the local complex molecular environment in vivo; nonetheless, this area is hardly explored. To address the relevance of such interactions with regard to structure and function, we have tested the effects of the therapeutic drug suramin on the membrane activity and antibacterial efficiency of CM15, a potent hybrid AMP. The results provided insight into a dynamic system in which peptide interaction with lipid bilayers is interfered with by the competitive binding of CM15 to suramin, resulting in an equilibrium dependent on peptide-to-drug ratio and vesicle surface charge. In vitro bacterial tests showed that when CM15⋅suramin complex formation dominates over membrane binding, antimicrobial activity is abolished. On the basis of this case study, it is proposed that small-molecule secondary structure regulators can modify AMP function and that this should be considered and could potentially be exploited in future development of AMP-based antimicrobial agents.
Identifiants
pubmed: 30720915
doi: 10.1002/cbic.201800801
pmc: PMC6618317
doi:
Substances chimiques
Anti-Infective Agents
0
Antimicrobial Cationic Peptides
0
Lipid Bilayers
0
antimicrobial hybrid peptide CM15
0
Suramin
6032D45BEM
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1578-1590Informations de copyright
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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