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Examination of methodology for the synthesis of cyclic thioether peptide libraries derived from linear tripeptides
Author(s) -
Roberts Kade D.,
Ede Nicholas J.
Publication year - 2007
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.904
Subject(s) - tripeptide , tetrapeptide , dimer , thioether , cyclic peptide , chemistry , peptide , combinatorial chemistry , stereochemistry , intramolecular force , peptide synthesis , alkylation , monomer , sequence (biology) , organic chemistry , biochemistry , catalysis , polymer
Work was undertaken to examine methodology for the cyclization of linear tripeptides on the solid phase via intramolecular S ‐alkylation using the Multipin ™ Solid‐Phase Peptide Synthesis platform. While previous work had shown that this chemistry could be used to efficiently cyclize linear tetrapeptide libraries, application of this synthetic strategy to the model linear tripeptide sequence Leu‐Ser‐Lys resulted in significant cyclic dimer formation. Ultimately, it was found that the addition of a large excess of lithium in the form of LiCl to the cyclization solution, significantly reduced cyclic dimer formation affording highly pure crude cyclic monomer. The application of this modified cyclization protocol to the preparation of cyclic peptide libraries was successfully demonstrated with the synthesis of a 20‐membered library 4 { 1–20 } based on the linear tripeptide sequence Leu‐ Xxx ‐Lys in which the position Xxx was varied with the standard 20 proteogenic residues. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.