Cyclic Peptides exhibit diverse biological activities, e.g. antibacterial, toxic, immunosuppressive or antitumor activity. In many cyclic peptides, conformational rigidity is further increased by disulfide bond formation. Cyclization of a peptide significantly enhances proteolytic stability. Furthermore, the resulting conformational restriction usually leads to better bioavailability and biological activity. The higher rigidity of a cyclic peptide compared to its linear counterpart results in enhanced binding to and selectivity for receptors or target molecules.

The regioselective formation of S-S-bonds presents the greatest synthetic challenge in the preparation of disulfide-bridged peptides, especially when multiple Cys residues are present. In these cases, orthogonal Cys protecting groups are required.

The innovative Msbh protecting group is stable to the deprotection conditions of most common cysteine PGs such as Mmt (monomethoxytrityl), Trt (trityl), Acm (acetylaminomethyl) or Phacm (phenylacetylaminomethyl). Moreover, it is stable to conditions applied in both Boc and Fmoc chemistry. Reduction of the sulfoxide to the sulfide renders the bond between the cysteine sulfhydryl group and the benzylic carbon of the Msbh group acid labile, and thus enables facile deprotection using TFA.

→ Iris Biotech also offers other Cys building blocks equipped with innovative protecting groups such as Phacm (phenylacetylaminomethyl). Find our 100 different Cysteine derivatives in our webshop!

→ Do you require more information about Cys building blocks and the formation of cyclic peptides? Order our brochure “Strategies and Building Blocks for the Synthesis of Cyclic Peptides” free of charge.

• Total Synthesis of Human Hepcidin through Regioselective Disulfide-Bond Formation by using the Safety-Catch Cysteine Protecting Group 4,4′-Dimethylsulfinylbenzhydryl; Z. Dekan, M. Mobli, M. W. Pennington, E. Fung, E. Nemeth and P. F. Alewood; Angewandte Chemie International Edition 2014; 53: 2931-2934. doi:10.1002/anie.201310103
• A new safety-catch protecting group and linker for solid-phase synthesis; S. Thennarasu and C.-F. Liu; Tetrahedron letters 2010; 51: 3218-3220. doi:http://dx.doi.org/10.1016/j.tetlet.2010.04.047
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• A safety-catch type of amide protecting group; M. Pátek and M. Lebl; Tetrahedron letters 1990; 31: 5209-5212. doi:http://dx.doi.org/10.1016/S0040-4039(00)97844-4
• The p-(methylsulfinyl)benzyl group: a trifluoroacetic acid (TFA)-stable carboxyl-protecting group readily convertible to a TFA-labile group; J. M. Samanen and E. Brandeis; The Journal of Organic Chemistry 1988; 53: 561-569. doi:10.1021/jo00238a016