Abstract
To speed drug discovery, we developed an approach for identification of individual peptides with a desired biological activity from a library containing millions of peptides. The approach uses sequential orthogonal release of chemically synthesized peptides from insoluble beads, followed by testing in solution. In this system, each bead within a library of beads has one peptide sequence, but peptide molecules are attached to the bead with three types of chemical linkers, including two linkers cleavable at different pH optima. An uncleavable linker keeps some peptide attached to the bead for sequencing positives from the solution assay. Applicability of this discovery technique was documented by identifying ligands for a monoclonal antibody and for the human platelet fibrinogen receptor, glycoprotein IIb/IIIa.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 11708-11712 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 90 |
| Issue number | 24 |
| State | Published - Dec 15 1993 |
| Externally published | Yes |
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Keywords
- Peptide library screening
ASJC Scopus subject areas
- General
- Genetics
Cite this
Discovery of biologically active peptides in random libraries : Solution-phase testing after staged orthogonal release from resin beads. / Salmon, Sydney E.; Lam, Kit; Lebl, Michal; Kandola, Anitha; Khattri, Parth S.; Wade, Shelly; Pátek, Marcel; Kocis, Petr; Krchnák, Viktor; Thorpe, David; Felder, Stephen.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 24, 15.12.1993, p. 11708-11712.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Discovery of biologically active peptides in random libraries
T2 - Solution-phase testing after staged orthogonal release from resin beads
AU - Salmon, Sydney E.
AU - Lam, Kit
AU - Lebl, Michal
AU - Kandola, Anitha
AU - Khattri, Parth S.
AU - Wade, Shelly
AU - Pátek, Marcel
AU - Kocis, Petr
AU - Krchnák, Viktor
AU - Thorpe, David
AU - Felder, Stephen
PY - 1993/12/15
Y1 - 1993/12/15
N2 - To speed drug discovery, we developed an approach for identification of individual peptides with a desired biological activity from a library containing millions of peptides. The approach uses sequential orthogonal release of chemically synthesized peptides from insoluble beads, followed by testing in solution. In this system, each bead within a library of beads has one peptide sequence, but peptide molecules are attached to the bead with three types of chemical linkers, including two linkers cleavable at different pH optima. An uncleavable linker keeps some peptide attached to the bead for sequencing positives from the solution assay. Applicability of this discovery technique was documented by identifying ligands for a monoclonal antibody and for the human platelet fibrinogen receptor, glycoprotein IIb/IIIa.
AB - To speed drug discovery, we developed an approach for identification of individual peptides with a desired biological activity from a library containing millions of peptides. The approach uses sequential orthogonal release of chemically synthesized peptides from insoluble beads, followed by testing in solution. In this system, each bead within a library of beads has one peptide sequence, but peptide molecules are attached to the bead with three types of chemical linkers, including two linkers cleavable at different pH optima. An uncleavable linker keeps some peptide attached to the bead for sequencing positives from the solution assay. Applicability of this discovery technique was documented by identifying ligands for a monoclonal antibody and for the human platelet fibrinogen receptor, glycoprotein IIb/IIIa.
KW - Peptide library screening
UR - http://www.scopus.com/inward/record.url?scp=0027142990&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027142990&partnerID=8YFLogxK
M3 - Article
C2 - 8265613
AN - SCOPUS:0027142990
VL - 90
SP - 11708
EP - 11712
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 24
ER -