The Safety-Catch Acid-Labile (SCAL)-Linker

Published on 19/07/2016

The SCAL linker offers superior chemical stability and permits a variety of orthogonal solid-phase approaches. It is fully compatible with the Fmoc-, Boc- and Alloc- strategies. Cleavage can be performed either by a simultaneous, or by a two-step reduction/acidolysis procedure to afford peptide amides.

The Safety-Catch Acid-Labile (SCAL)-Linker

The correct choice of linker is pivotal for the success of a solid-phase synthesis. Commonly, linkers for solid-phase peptide synthesis are cleaved under acidic or basic conditions. This usually limits the possible protecting group strategies to either the Fmoc or the Boc strategy, respectively. Also the choice of side-chain protecting groups is restricted.

Iris Biotech now offers the innovative Safety-Catch Acid-Labile (SCAL) linker, using the 4,4'-dimethylsulfinylbenzhydryl (Msbh) moiety as cleavable element. The SCAL linker is, until being activated by reduction, stable to all but the harshest acidic conditions, as well as many basic conditions. Furthermore, the SCAL linker shows stability towards some reductive conditions such as hydrostannolysis, or Alloc deprotection conditions.

Consequently, SPPS on a solid support equipped with the SCAL linker can be performed by using the Fmoc-, the Boc- or the Alloc-strategy.

Peptide Synthesis on the SCAL linker

Cleavage can occur either by using a two-step procedure of reduction and subsequent acidolysis (shown below), or by a one-pot reductive acidolysis (e.g. using SiCl₄/anisole/TFA). Cleavage of the peptide from the solid support affords a C-terminal peptide amide.

Cleavage of the SCAL linker by a two-step reduction/acidolysis procedure

→ Iris Biotech also offers a novel Cysteine building block employing the safety-catch Msbh moiety as side-chain protecting group. This building block can be used for the regioselective formation of disulfide bonds in Cys-rich peptides.
→ Visit our webshop to find a huge variety of rare and innovative Amino Acid building blocks.
→ Do you require Coupling Reagents or Solvents for SPPS? Find everything you need and more in our Reagents section.
→ Iris Biotech also offers many different Resins for solid-phase synthesis.
→ For your convenience, we provide our customers with the 20 standard Fmoc-amino acids as pre-packed cartridges for ABI, CEM and PTI peptide synthesizers.

References:

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
A Reductive Acidolysis Final Deprotection Strategy in Solid Phase Peptide Synthesis Based on Safety-Catch Protection; T. Kimura, T. Fukui, S. Tanaka, K. Akaji and Y. Kiso; CHEMICAL & PHARMACEUTICAL BULLETIN 1997; 45: 18-26. doi:10.1248/cpb.45.18
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