Evidence map›Paper›PMID 31427820›Full record

ArticleNature biotechnology2019

Design of stapled antimicrobial peptides that are stable, nontoxic and kill antibiotic-resistant bacteria in mice.

Rida Mourtada, Henry D Herce, Daniel J Yin, Jamie A Moroco, Thomas E Wales, John R Engen, Loren D Walensky

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed
20.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

135 citing papers in PubMed, 284 citations in OpenAlex.

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  8. De Novo Multi-Mechanism Antimicrobial Peptide Design via Multimodal Deep Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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75 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Rida MourtadaDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Henry D HerceDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Daniel J YinDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jamie A MorocoDepartment of Chemistry and Chemical Biology, Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA, USA.
Thomas E WalesDepartment of Chemistry and Chemical Biology, Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA, USA.
John R EngenDepartment of Chemistry and Chemical Biology, Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6918-9476
Loren D WalenskyDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. loren_walensky@dfci.harvard.edu.ORCID http://orcid.org/0000-0002-0869-2334
Dana-Farber Cancer Institute · USNortheastern University · USHarvard–MIT Division of Health Sciences and Technology · US

Funding

Dissecting and Targeting Deregulated Mitochondrial Apoptosis in Human CancerR35CA197583 · NCI · DANA-FARBER CANCER INST · PI Loren David Walensky · 2015 to 2026
$12.5M
Extending the applications of hydrogen exchange mass spectrometryR01GM101135 · NIGMS · NORTHEASTERN UNIVERSITY · PI ENGEN, JOHN R · 2012 to 2015
$1.2M
Engineering damage associated molecular patterns to promote tissue regenerationF32EB025688 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SADTLER, KAITLYN NOELLE · 2018 to 2018
$55k
NCI NIH HHS R35 CA197583NIBIB NIH HHS F32 EB025688NIGMS NIH HHS R01 GM101135
6 · The paper itself

Abstract

The clinical translation of cationic α-helical antimicrobial peptides (AMPs) has been hindered by structural instability, proteolytic degradation and in vivo toxicity from nonspecific membrane lysis. Although analyses of hydrophobic content and charge distribution have informed the design of synthetic AMPs with increased potency and reduced in vitro hemolysis, nonspecific membrane toxicity in vivo continues to impede AMP drug development. Here, we analyzed a 58-member library of stapled AMPs (StAMPs) based on magainin II and applied the insights from structure-function-toxicity measurements to devise an algorithm for the design of stable, protease-resistant, potent and nontoxic StAMP prototypes. We show that a lead double-stapled StAMP named Mag(i+4)1,15(A9K,B21A,N22K,S23K) can kill multidrug-resistant Gram-negative pathogens, such as colistin-resistant Acinetobacter baumannii in a mouse peritonitis-sepsis model, without observed hemolysis or renal injury in murine toxicity studies. Inputting the amino acid sequences alone, we further generated membrane-selective StAMPs of pleurocidin, CAP18 and esculentin, highlighting the generalizability of our design platform.

Indexed as

AnimalsAnti-Bacterial AgentsAntimicrobial Cationic PeptidesBacteriaCell LineDrug DesignDrug Resistance, BacterialErythrocytesFemaleHumansMaleMiceMice, Inbred C57BLPeritonitisSepsisAnti-Bacterial AgentsAntimicrobial Cationic Peptides

Identifiers

PMID31427820
PMCPMC7437984
OpenAlexW2967078590

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.