Two distinct amphipathic peptide antibiotics with systemic efficacy.
Amino Acid Sequence
Animals
Anti-Bacterial Agents
/ chemistry
Antimicrobial Cationic Peptides
/ chemistry
Bacteria
/ drug effects
Bacterial Infections
/ drug therapy
Biofilms
/ drug effects
Cell Membrane
/ metabolism
Databases, Protein
Drug Design
Drug Resistance, Bacterial
/ drug effects
Humans
Hydrophobic and Hydrophilic Interactions
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microbial Sensitivity Tests
Structure-Activity Relationship
Treatment Outcome
NMR
antibiotic resistance
nephrotoxicity
peptide antibiotics
systemic efficacy
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
11 08 2020
11 08 2020
Historique:
pubmed:
30
7
2020
medline:
2
10
2020
entrez:
30
7
2020
Statut:
ppublish
Résumé
Antimicrobial peptides are important candidates for developing new classes of antibiotics because of their potency against antibiotic-resistant pathogens. Current research focuses on topical applications and it is unclear how to design peptides with systemic efficacy. To address this problem, we designed two potent peptides by combining database-guided discovery with structure-based design. When bound to membranes, these two short peptides with an identical amino acid composition can adopt two distinct amphipathic structures: A classic horizontal helix (horine) and a novel vertical spiral structure (verine). Their horizontal and vertical orientations on membranes were determined by solid-state
Identifiants
pubmed: 32723829
pii: 2005540117
doi: 10.1073/pnas.2005540117
pmc: PMC7431008
doi:
Substances chimiques
Anti-Bacterial Agents
0
Antimicrobial Cationic Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19446-19454Subventions
Organisme : NIAID NIH HHS
ID : R01 AI105147
Pays : United States
Organisme : NIAID NIH HHS
ID : R03 AI128230
Pays : United States
Organisme : NIH HHS
ID : R24 OD018546
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH062261
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI105147
Pays : United States
Déclaration de conflit d'intérêts
Competing interest statement: The authors have submitted worldwide patent applications for the reported new peptides.
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