Side chain functionalities in Fmoc solid phase synthesis are routinely protected by mild acid labile protecting groups. The foremost choice among these are t-butyl (t-Bu) and trityl (Trt) based groups. In certain situations, the trityl based groups offer distinct advantages over the t-butyl based groups.
The following advantages occur:
- If a side chain derivatized peptide is required, for instance on a Ser or Lys residue, and this side chain is protected with a trityl or modified trityl group, then this can be selectively deprotected in the presence of global side chain protection by t-butyl based groups. The modification of the side chain can then be made.
- The advantages of using trityl versus t-butyl is clearly shown with a range of model peptides consisting of Ser,Thr,Met,Lys and Trp where t-butyl based groups were compared with trityl groups. The relatively mild acidolysis of the trityl groups gave much purer peptides with these difficult amino acid sequences (1).
- It has also been shown that when making deca-serine and comparing trityl protection to t-butyl for side chain protection, the Fmoc group was difficult to remove in the t-butyl series (2). Also in a synthesis of a peptide containing greater than 20 amino acids, there was no Kaiser color obtained when attempting to deprotect a Fmoc-Thr(t-Bu) peptide after approximately 15 residues are in the assembly. This suggests that the Fmoc group had not been removed fully (3).
These observations show that trityl based side chain protection can be used advantageously over t-butyl based protection in many peptides. Trityl side chain protected Fmoc amino acids including Fmoc-Ser(Trt), Fmoc-Thr(trt) and 25 others are readily available in various quantities, in both the D and L configuration from CBL. Please contact us to request more information on CBL technologies or to obtain product information.
- Barlos, K. Gatos, D. Koutsogianni, S. Peptide Res. 51, 194-200 (1998).
- Tong, X. Ichihara, K. Tian, Q. Hong, A. Peptide Revolution:Genomics, Proteomics, and Therapeutics. American Peptide Society, 2003.
- Dr. Eric Atherton, unpublished results