Product of the Month: Fmoc-L-Cys(Dpm)-OH

Published on 28/10/2013

Any amino acid can be functionalized on the N-terminus with oxalic acid and on the C-terminus with hydrazine, in order to form a so-called NXO building block. Through this double modification N and C terminus will be inverted, which provides interesting structural options for peptidomimetics.

For the targeted synthesis of two disulfide bridges so far the protecting group combination Trt (trityl) and Mmt (4-methoxytrityl) has been used. As Mmt can be removed with 1% TFA and Trt requires higher concentration for removal, in principal a good orthoganality is given.
It was, however, observed in large scale synthesis that with 1% TFA still significant amounts of Mmt stay on the cysteine, while already significant parts of Trt have cleaved. Therefore, there is still room for improvement for cost effective synthesis.

Alberico et al. have studied and developed many new protecting groups where Dpm (diphenylmethyl) and Mmt have turned out to be an ideal pair:

Mmt:	clearage with 5% TFA will reliably deprotect all Cys(Mmt)
Dpm:	requires min. 60% for cleavage, therefore 90% TFA in DCM is a safe and fast procedure to liberate all Cys(Dpm).

Relevant latest literature about cysteine protection:

Knut Adermann, Kleomenis Barlos; Chapter 6.2 Regioselective Disulfide Formation in Oxidative Folding of Peptides and Proteins, Editor(s): Luis Moroder, Johannes Buchner, 2008, 297-317. DOI:10.1039/9781847559265-00297.
Acid-Labile Cys-Protecting Groups for the Fmoc/tBu Strategy: Filling the Gap; Miriam Góngora-Benítez, Lorena Mendive-Tapia, Iván Ramos-Tomillero, Arjen C. Breman, Judit Tulla-Puche, and Fernando Albericio; Org. Lett. 2012; 14(21): 5472-5475. DOI 10.1021/ol302550p.

Fmoc-L-Cys(Dpm)-OH is available in multi KG scale and can easily be up-scaled for bulk productions: