CLIPS cyclization

As an expert in constrained peptides, Pepscan has also developed a proprietary, highly versatile constaining technology, called CLIPS (Chemical Linkage of Peptides onto Scaffolds; WO2004/077062).

CLIPS technology involves the cyclization of linear peptides via reaction of thiol-functionalities of the cysteines with a small rigid entity. This anchor reacts exclusively with thiols and attaches to the peptide via covalent bonds. The CLIPS cyclization technology is unique for its versatility and ease of application. The cyclization reaction lasts no longer than 30 min, runs at room temperature and does not require any sort of catalysis.

Schematic representation of a “1-CLIPS” reaction (left panel), and different CLIPS-based topologies (2-CLIPS & 3-CLIPS loops)

Schematic representation of a “1-CLIPS” reaction (left panel), and different CLIPS-based topologies (2-CLIPS & 3-CLIPS loops)

Advantages of the CLIPS cyclization technology over other cyclization methods are:

  • Applicable to mono- and bicyclic peptides
  • Cyclization via formation of stable covalent thio-ether bond
  • Compatible with the presence of side-chain-unprotected amino acids
  • Tailoring via a toolbox of over 70 scaffolds of different polarity, rigidity, solubility, functionality, and ‘SS-spanning’ distance
CLIPS

A small selection of CLIPS scaffolds, tailoring for different topologies, S-S spanning distances, physicochemical properties or functionalities. WS: watersoluble moiety; FG: functional group