CLIPS Cyclization
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CLIPS Cyclization

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CLIPS (Chemical Linkage of Peptides onto Scaffolds) Cyclization is an integrated technology that combines chemical linkage of a linear peptide to a synthetic scaffold with conformational fixation of the peptide. The reaction conditions of CLIPS Cyclization are extremely mild (<15 min at 258, aqueous-buffered solutions, pH 7.8) and fully compatible with un/deprotected side-chain functionalities (NH2, COOH, OH, imidazol, etc.) in the peptide. The reaction of CLIPS Cyclization is extremely clean and fast. It runs very well with linear peptides which have 2–30 amino acids. The reaction is compatible with all possible unprotected side-chain functionalities (except for free cysteine). Therefore, CLIPS Cyclization avoids the need for complex synthetic strategies and this makes the reaction highly versatile with a very wide scope. The ingle-, double-, and triple-loop peptide constructs by treating di-, tri-, and tetracysteine containing peptides with bis, tris-, and tetrakis(bro- momethyl)- benzene de-rivativnetse.


Fig.1 The schematic representation of CLIPS Cyclization (Timmerma et al. 2005)

Application of CLIPS Cyclization

As a technology for peptide cyclization, the CLIPSTM (Chemically Linked Peptides on Scaffolds) has been applied successfully in identifying the epitope on human CD20 and reconstructing the conformational epitope on follicle stimulating hormone.
The CLIPS-peptides has the following characteristics:

  1. Single-constrained CLIPS-peptides generally show large animal-to-animal variations, most likely the result of insufficient preorganization.
  2. It is worth noting that the CLIPS−peptides are relatively large cargos.
  3. The CLIPS architecture afforded peptides with long-term proteolytic stability which promoted uptake efficiency.

In summary, the application of CLIPS-technology may have the broad applicability for the reconstruction of other protein surfaces with even higher structural complexity, such as, the transmembrane proteins (TKR’s, GPCR’s), or certain viral proteins (HIV).

Available Services

CLIPS Cyclization can be used for conformational fixation of free peptides in solution, while it also applies to solid-phase attached peptides in microarrays used for antibody-screening. CLIPS-technology is orthogonal to and fully compatible with oxidative disulfide bond formation, providing a new idea for peptide synthesis. We have many years of experience in providing peptide synthesis services. Creative Peptides has developed a toolbox of many different types of fully synthetic, tailor-made CLIPS scaffolds, varying mainly in size, polarity, rigidity, solubility, functionality, and ‘SS-spanning’ distance. Based on our excellent technology, we are your best choice for producing custom peptides on time and on budget. Our experienced scientists will tailor the most appropriate methods and 100% guaranteed service for customers. Every step of peptide synthesis is subject to Creative Peptides’ stringent quality control. Typical delivery specifications include:

  1. HPLC chromatogram
  2. Mass spec analysis
  3. Synthesis report
  4. Certificate of Analyses

1. Timmerman, P., Beld, J., Puijk, W. C., & Meloen, R. H. (2005). Rapid and quantitative cyclization of multiple peptide loops onto synthetic scaffolds for structural mimicry of protein surfaces. ChemBioChem, 6(5), 821-824.
2. Timmerman, P., Puijk, W. C., & Meloen, R. H. (2007). Functional reconstruction and synthetic mimicry of a conformational epitope using CLIPS™ technology. Journal of Molecular Recognition: An Interdisciplinary Journal, 20(5), 283-299.
3. Wallbrecher, R., Depré, L., Verdurmen, W. P., Bovée-Geurts, P. H., van Duinkerken, R. H., Zekveld, M. J & Brock, R. (2014). Exploration of the design principles of a cell-penetrating bicylic peptide scaffold. Bioconjugate chemistry, 25(5), 955-964.

If you have any peptide synthesis requirement in mind, please do not hesitate to contact us at . We will endeavor to provide highly satisfying products and services.
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