Generation of Multiuse Peptide Libraries for Functional Screenings
| Abstract |
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The range of applications for large-scale synthetic molecule libraries (1–7) can be expanded if the constituents can be liberated locally from their supporting matrix in a controlled manner so that
fractions are available for multiple independent tests, free of interference from other constituents of the library. A method
was developed to study the functional responses arlsing from individual constituent beads in a synthetic combinatorial peptide
library by introducing the multiuse peptide library (MUPL) concept (8). In the MUPL method (
Fig. 1
), peptides are liberated from their supports in a dry state so that the problem of signal interference caused by mixing of
peptlde molecules, particularly agonists and antagonists, is avoided. In addition, the peptides are released rn a controlled
manner so that fractions are available for repetitive screens, thus elimmating the need for iterative library analysis and
resynthesis Since the liberated constituents are not constrained by the tethered linkers, the molecules are free to assume
their native conformations. These unique features of an MUPL has enabled the use of large-scale synthetic molecule libraries
for functional screening (8–10).
Fig. 1.
Schematic representation of the generation of multiuse peptide libraries.
Affiliation(s): (2) Department of Cellular Biochemistry, Glaxo-Wellcome, Inc., NC
(3) Boyer Center for Molecular Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT
(3) Boyer Center for Molecular Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT
Book Title: Combinatorial Peptide Library Protocols
Series: Methods in Molecular Biology | Volume: 87 | Pub. Date: Dec-23-1997 | Page Range: 107-118 | DOI: 10.1385/0-89603-392-9:107
Subject: Protein Science
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