Seamless bead to microarray screening: rapid identification of the highest affinity protein ligands from large combinatorial libraries.
Several approaches have been developed for screening combinatorial libraries or collections of synthetic molecules for agonists or antagonists of protein function, each with its own advantages and limitations. In this report, we describe an experimental platform that seamlessly couples massively parallel bead-based screening of one-bead one-compound combinatorial libraries with microarray-based quantitative comparisons of the binding affinities of the many hits isolated from the bead library. Combined with other technical improvements, this technique allows the rapid identification of the best protein ligands in combinatorial libraries containing millions of compounds without the need for labor-intensive resynthesis of the hits.
Astle
John M
JM
Departments of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9185, USA.
Simpson
Levi S
LS
Huang
Yong
Y
Reddy
M Muralidhar
MM
Wilson
Rosemary
R
Connell
Steven
S
Wilson
Johnnie
J
Kodadek
Thomas
T
D020650:Combinatorial Chemistry Techniques / Q000191:economics / Q000379:methods*; D008024:Ligands; D008280:Magnetics; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D040081:Protein Array Analysis; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors
D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D011506:Proteins