Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Designing β-hairpin peptide macrocycles for antibiotic potential

Justin R. Randall, Cory D. DuPai, T. Jeffrey Cole, Gillian Davidson, Kyra E. Groover, View ORCID ProfileClaus O. Wilke, Bryan W. Davies
doi: https://doi.org/10.1101/2022.06.21.497034
Justin R. Randall
1Department of Molecular Biosciences, University of Texas at Austin; Austin, TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cory D. DuPai
1Department of Molecular Biosciences, University of Texas at Austin; Austin, TX, USA
2Department of Integrative Biology, University of Texas at Austin; Austin, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
T. Jeffrey Cole
1Department of Molecular Biosciences, University of Texas at Austin; Austin, TX, USA
2Department of Integrative Biology, University of Texas at Austin; Austin, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gillian Davidson
1Department of Molecular Biosciences, University of Texas at Austin; Austin, TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyra E. Groover
1Department of Molecular Biosciences, University of Texas at Austin; Austin, TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Claus O. Wilke
2Department of Integrative Biology, University of Texas at Austin; Austin, Texas, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Claus O. Wilke
Bryan W. Davies
1Department of Molecular Biosciences, University of Texas at Austin; Austin, TX, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: bwdavies@austin.utexas.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Peptide macrocycles are a rapidly emerging new class of therapeutic, yet the design of their structure and activity remains challenging. This is especially true for those with β-hairpin structure due to weak folding properties and a propensity for aggregation. Here we use proteomic analysis and common antimicrobial features to design a large peptide library with macrocyclic β-hairpin structure. Using an activity-driven high-throughput screen we identify dozens of peptides killing bacteria through selective membrane disruption and analyze their biochemical features via machine learning. Active peptides contain a unique constrained structure and are highly enriched for cationic charge with arginine in their turn region. Our results provide a synthetic strategy for structured macrocyclic peptide design and discovery, while also elucidating characteristics important for β-hairpin antimicrobial peptide activity.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted June 22, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Designing β-hairpin peptide macrocycles for antibiotic potential
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Designing β-hairpin peptide macrocycles for antibiotic potential
Justin R. Randall, Cory D. DuPai, T. Jeffrey Cole, Gillian Davidson, Kyra E. Groover, Claus O. Wilke, Bryan W. Davies
bioRxiv 2022.06.21.497034; doi: https://doi.org/10.1101/2022.06.21.497034
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Designing β-hairpin peptide macrocycles for antibiotic potential
Justin R. Randall, Cory D. DuPai, T. Jeffrey Cole, Gillian Davidson, Kyra E. Groover, Claus O. Wilke, Bryan W. Davies
bioRxiv 2022.06.21.497034; doi: https://doi.org/10.1101/2022.06.21.497034

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biochemistry
Subject Areas
All Articles
  • Animal Behavior and Cognition (3609)
  • Biochemistry (7590)
  • Bioengineering (5533)
  • Bioinformatics (20833)
  • Biophysics (10347)
  • Cancer Biology (7998)
  • Cell Biology (11663)
  • Clinical Trials (138)
  • Developmental Biology (6619)
  • Ecology (10227)
  • Epidemiology (2065)
  • Evolutionary Biology (13648)
  • Genetics (9557)
  • Genomics (12860)
  • Immunology (7932)
  • Microbiology (19576)
  • Molecular Biology (7678)
  • Neuroscience (42194)
  • Paleontology (309)
  • Pathology (1259)
  • Pharmacology and Toxicology (2208)
  • Physiology (3272)
  • Plant Biology (7064)
  • Scientific Communication and Education (1296)
  • Synthetic Biology (1953)
  • Systems Biology (5435)
  • Zoology (1119)