Thank you for your comments. I haven't done an in-depth study on the
reactivity of the thioester, but I have routinely made N-terminally
mercaptoacetylated peptides using NMM/HBTU. My ES-MS and HPLC analysis
indicate that mercaptoacetic acid is stable to conditions of activation,
coupling, and TFA cleavage using these normal FMOC conditions. Note that in my
case, the mercaptoacetic acid acts always as an N-terminal cap, so it is not
exposed to piperidine. I did a small test once with my mercaptoacetylated
peptide mixed in neat piperidine and found 25% debenzoylation after 4h, so it
definitely is not suitable as a general thiol protecting group for SPPS.
Richard Laursen wrote:
> Gary,
>
> The S-benZYL group has been widely used for protecting the thiol group of
> cysteine in BOC chemistry, but I am not aware of the the use of S-benZOYL
> (which does not mean that it hasn't been used--just my ignorance).
> S-Benzoylmercaptoacetic acid is a thioester and is therefore very unstable
> under alkaline conditions or in the presence of nucleophiles. In fact
> thioesters were used in the olden days for making peptide bonds. I would
> worry about it benzoylating the alpha-amino group of your peptide when you
> couple S-benzoylmercaptoacetic acid to it. On the other hand, if you
> activate the carboxyl group of S-benzoylmercaptoacetic acid sufficiently
> (carbodiimide or symmetrical anhydride methods? maybe even the acid
> chloride) it might outcompete the benzoylation reaction. I would avoid
> activation with reagents that use hydroxybenzotriazole, since HOBt probably
> would react with the thioester making the benzoyl group even more reactive.
> I believe that the thioester would survive the acidic conditions needed to
> cleave the peptide from the resin.
>
> Maybe someone out there has some firsthand experience.
>
> Richard Laursen
>
> >Dear ABRFers,
> >
> >I am preparing peptides using a benzoylated derivative of mercaptoacetic
> >acid, a cyseine analog. I have heard rumous that s-benzoyl protected
> >cysteine was used as a protecting group for boc chemistry in the distant
> >past. Are there any old-timers out there who confirm or deny this? I
> >would appreciate any references if you have some handy.
> >
> >Sincerely,
> >
> >Gary Van Domselaar
> >
> >Gary Van Domselaar gvd@redpoll.pharmacy.ualberta.ca
> >Faculty of Pharmacy Phone: (403) 492-4493
> >University of Alberta FAX: (403) 492-5305
> >Edmonton, Alberta, Canada
>
> Richard A. Laursen
> Department of Chemistry
> Boston University
> 590 Commonwealth Ave.
> Boston, MA 02215
> Tel (617) 353-2491; FAX (617) 353-6466
> email: <laursen@bu.edu>