One of the most versatile cysteine side chain protecting groups in Fmoc based solid phase synthesis is the 4-Methoxytrityl group (Mmt). The protecting group can be very readily introduced onto the cystine (cys) side chain by the reaction with 4-methoxytrityl chloride with cysteine hydrochloride hydrate. The Mmt group is highly acid sensitive (1). Mmt can be completely removed by 1% trifluoroacetic acid (TFA) in dichloromethane (DCM) / triethylsilane (TES) (95:5) in thirty minutes. In comparison, only 4-5% of the trityl group is removed under these conditions when using trityl protected cystine.
When the Mmt protecting group is used in combination with a 2-chlorotrityl resin support and t-butyl side chain protection for other amino acids, the peptide can be removed from the support, the Mmt group removed and the -S-S- bridge and made directly while retaining side chain protection (1).. As a result, it is compatible with other cystine side chain protecting groups such as S-acetamidomethyl (Acm).
A novel example of the utility of the Mmt protecting group is on a chain cyclisation reaction to form a disulphide. When used in combination with Cys(StBu) in the same chain, this group can be removed by reduction and converted to Cys(5-Npys) derivative by reaction with 2,2″dithiodi(5nitro)pyridine (DTNP). Treatment of the resin with 1% TFA liberates the thiol which then reacts with the activated Cys(5-Npys) to give the disulphide (2) .
Fmoc-Cys(Mmt)OH, as well as Fmoc protected amino acids and loaded resins, are readily available from CBL from the small to large scale. Please contact us to request more information on CBL technologies, or to obtain product information.
1.) Barlos, D. Gatos, O. Hatzi, N. Koch, S. Koutsogianni. Int. J. Peptide Protein Res. 47. 1996, 148-lS3
2.) Amit K. Galande,, Ralph Weissleder, and, Ching-Hsuan Tung Journal of Combinatorial Chemistry 2005 7 (2), 174-177