posted on 2022-07-08, 09:43authored byK. P. Nandhini, Fernando Albericio, Beatriz G. de la Torre
Fmoc and Boc group are the two main groups used to protect
the
α-amino function in Solid-Phase Peptide Synthesis (SPPS). In
this regard, the use of the Mmsb linker allows the combination of
these two groups. Peptide-O-Mmsb-Resin is stable to the piperidine
and trifluoroacetic acid (TFA) treatment used to remove Fmoc and Boc,
respectively. The peptide is detached in a two-step protocol, namely
reduction of the sulfoxide to the sulfide with Me3SiCl
and Ph3P, and then treatment with TFA. The advantage of
this strategy has been demonstrated by the following: preparation
of peptide with no diketopiperazine formation in sequences prone to
this side reaction; on-resin cyclization without the concourse of
common organic reagents such as Pd(0) but of difficult use in a biological
laboratory; and on-resin disulfide formation in a total side-chain
unprotected peptide. The use of Mmsb linker together with Msib (4-(methylsulfinyl)benzyl)
and Msbh (4,4′-bis(methylsulfinyl)benzhydryl) described in
the accompanying manuscript add a fourth dimension to the SPPS protecting
group scheme.