Thanks to their high affinity and biochemical stability, cyclic peptides are at the forefront in drug research and discovery of ligands for protein purification. Combinatorial libraries of cyclic peptides are powerful tools in developing novel leads for target proteins. The step of sequence identification, however, is a serious issue in the process of discoverying cyclic peptides. While the determination of linear sequences is straightforward, the sequencing of cyclic molecules is much more challenging. We therefore propose a method for the synthesis of a combinatorial library of reversible cyclic peptides. Each molecule comprises two cleavable linkers that allow extracting the peptide sequence from the selected beads upon treatment with a cleaving agent. The linearized peptide is released from the support to the liquid phase and is finally sequenced by single stage MS/MS. This library is a very promising tool for the discovery of affinity ligands and drugs.

Novel reversible cyclic peptides for the discovery of affinity ligands

245th National Meeting (2013)

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