Wu, YutengZorzi, AlessandroWilliams, JackHeinis, Christian2020-03-282020-09-072020-03-282020-03-0710.1039/c9cc09247ahttps://infoscience.epfl.ch/handle/20.500.14299/167697WOS:000519216400019Combinatorial cyclization of hundreds to thousands of random linear peptides by structurally diverse chemical linkers offers access to large macrocyclic compound libraries. A bottleneck in the development of such libraries is the preparation of large numbers of short random linear peptides. Herein, we present a tag-based strategy that is not dependent on a throughput-limiting chromatographic purification step and thus enables parallel production of short peptides. In brief, peptides are synthesized on solid phase as conjugates with a disulfide-linked Cys-Gly-Arg-Trp tetra-peptide tag. The charged arginine residue in the tag allows for purification of the peptides by diethyl ether-precipitation and the tryptophan allows for quantification of the product by absorption measurement. Addition of a reducing agent releases the short peptides from the tag. The released sulfhydryl group in the peptide can readily be used for cyclization of the peptide library with bis-electrophilic linker reagents.Chemistry, MultidisciplinaryChemistrycyclic-peptidesselectiontext::journal::journal article::research article