Journal of Biomolecular Screening

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
1087057108314651v1
13/3/202    most recent
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Google Scholar
Google Scholar
Right arrow Articles by Hämäläinen, M. D.
Right arrow Articles by Björsne, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hämäläinen, M. D.
Right arrow Articles by Björsne, M.
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?
This version was published on March 1, 2008
Journal of Biomolecular Screening, Vol. 13, No. 3, 202-209 (2008)
DOI: 10.1177/1087057108314651

Label-Free Primary Screening and Affinity Ranking of Fragment Libraries Using Parallel Analysis of Protein Panels

Markku D. Hämäläinen

GE Healthcare Biosciences, R&D, Uppsala, Sweden, markku.hamalainen{at}ge.com

Andrei Zhukov

GE Healthcare Biosciences, R&D, Uppsala, Sweden

Maria Ivarsson

GE Healthcare Biosciences, R&D, Uppsala, Sweden

Tomas Fex

AstraZeneca R&D, Mölndal, Sweden

Johan Gottfries

AstraZeneca R&D, Mölndal, Sweden

Robert Karlsson

GE Healthcare Biosciences, R&D, Uppsala, Sweden

Magnus Björsne

AstraZeneca R&D, Mölndal, Sweden

The authors present fragment screening data obtained using a label-free parallel analysis approach where the binding of fragment library compounds to 4 different target proteins can be screened simultaneously using surface plasmon resonance detection. They suggest this method as a first step in fragment screening to identify and select binders, reducing the demanding requirements on subsequent X-ray or nuclear magnetic resonance studies, and as a valuable "clean-up" tool to eliminate unwanted promiscuous binders from libraries. A small directed fragment library of known thrombin binders and a general 500-compound fragment library were used in this study. Thrombin, blocked thrombin, carbonic anhydrase, and glutathione-S-transferase were immobilized on the sensor chip surface, and the direct binding of the fragments was studied in real time. Only 12 µg of each protein is needed for screening of a 3000-compound fragment library. For screening, a binding site-blocked target as reference facilitates the identification of binding site-selective hits and the signals from other reference proteins for the elimination of false positives. The scope and limitations of this screening approach are discussed for both target-directed and general fragment libraries. (Journal of Biomolecular Screening 2008:202-209)

Key Words: label-free screening • fragment library • protein • high-throughput screening


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?