Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers

W. Seth Horne, Lisa M. Johnson, Thomas J. Ketas, Per Johan Klasse, Min Lu, John P. Moore, and Samuel H. Gellman
PNAS first published August 17, 2009; https://doi.org/10.1073/pnas.0902663106
W. Seth Horne
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa M. Johnson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas J. Ketas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Per Johan Klasse
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Min Lu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John P. Moore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Samuel H. Gellman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: gellman@chem.wisc.edu
  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Abstract

Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining α- and β-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that α/β-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic α/β-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived α-peptides. An optimized α/β-peptide is far less susceptible to proteolytic degradation than is an analogous α-peptide. Our findings show how a two-stage design approach, in which sequence-based α→β replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.

  • alpha/beta-peptides
  • HIV
  • protein folding
  • protein–protein interactions

Footnotes

  • 1To whom correspondence should be addressed. E-mail: gellman{at}chem.wisc.edu
  • Author contributions: W.S.H., L.M.J., P.J.K., M.L., J.P.M., and S.H.G. designed research; W.S.H., L.M.J., T.J.K., and M.L. performed research; W.S.H., L.M.J., P.J.K., M.L., J.P.M., and S.H.G. analyzed data; and W.S.H. and S.H.G. wrote the paper.

  • Edited by David Baker, University of Washington, Seattle, WA, and approved July 2, 2009

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

Next
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers
W. Seth Horne, Lisa M. Johnson, Thomas J. Ketas, Per Johan Klasse, Min Lu, John P. Moore, Samuel H. Gellman
Proceedings of the National Academy of Sciences Aug 2009, pnas.0902663106; DOI: 10.1073/pnas.0902663106

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers
W. Seth Horne, Lisa M. Johnson, Thomas J. Ketas, Per Johan Klasse, Min Lu, John P. Moore, Samuel H. Gellman
Proceedings of the National Academy of Sciences Aug 2009, pnas.0902663106; DOI: 10.1073/pnas.0902663106
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 118 (3)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Large piece of gold
News Feature: Tracing gold's cosmic origins
Astronomers thought they’d finally figured out where gold and other heavy elements in the universe came from. In light of recent results, they’re not so sure.
Image credit: Science Source/Tom McHugh.
Dancers in red dresses
Journal Club: Friends appear to share patterns of brain activity
Researchers are still trying to understand what causes this strong correlation between neural and social networks.
Image credit: Shutterstock/Yeongsik Im.
Yellow emoticons
Learning the language of facial expressions
Aleix Martinez explains why facial expressions often are not accurate indicators of emotion.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490