Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Click here to register for free online access

Sign In to gain access to subscriptions and/or personal tools.
Journal of Biomolecular Screening
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
1087057107310216v1
12/8/1092    most recent
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via ISI Web of Science (2)
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Herman, R. E.
Right arrow Articles by Johnson, P. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Herman, R. E.
Right arrow Articles by Johnson, P. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Phage Display Screening of Epithelial Cell Monolayers Treated with EGTA: Identification of Peptide FDFWITP that Modulates Tight Junction Activity

Richard E. Herman

Nastech Pharmaceutical Company, Inc., Bothell, Washington

Ekaterina G. Makienko

Nastech Pharmaceutical Company, Inc., Bothell, Washington

Mary G. Prieve

Nastech Pharmaceutical Company, Inc., Bothell, Washington

Mark Fuller

Nastech Pharmaceutical Company, Inc., Bothell, Washington

Michael E. Houston, Jr

Nastech Pharmaceutical Company, Inc., Bothell, Washington, mhouston{at}nastech.com

Paul H. Johnson

Nastech Pharmaceutical Company, Inc., Bothell, Washington

Phage display was used to screen for peptides that modulate the activity of epithelial cell tight junctions. Panning with a phage library that displays random 7-mers was performed using monolayers of human bronchial epithelial cells (16HBE14o—) treated with a calcium chelator, ethylene glycol-bis(2-aminoethylether)- N, N, N', N'-tetraacetic acid (EGTA), to increase accessibility to the junctional complex/paracellular space, followed by subtractive panning. A novel peptide, FDFWITP, identified as a potential tight junction modulator, was synthesized in linear and cyclic forms with lysine residues added to improve solubility. The cyclic form of the peptide reduced transepithelial electrical resistance (TER) in a concentration-dependent manner (80% reduction at 100 µM and 95% reduction at 500 µM) and was reversible within 2 h; the linear form only affected TER at the highest concentration. Interestingly, the constrained peptide did not increase permeation of the model small molecule, fluorescein. The highly selective activity of FDFWITP supports the hypothesis that ions and small molecules may be transported paracellularly across tight junctions by separate pathways. (Journal of Biomolecular Screening 2007:1092-1101)

Key Words: peptide phage display • tight junction • epithelial barrier • claudin • calcium chelation • paracellular ion permeation

This version was published on December 1, 2007

Journal of Biomolecular Screening, Vol. 12, No. 8, 1092-1101 (2007)
DOI: 10.1177/1087057107310216
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?