Re: ProtSeq and MS: Prot modification

Richard Laursen (laursen@bu.edu)
Tue, 28 Jul 1998 17:40:24 -0500

The loss of 48 daltons corresponds to the loss of CH3-SH, which could give
dehydroaminobutyric acid as you suggest, but it could also give a cyclized
product, such as the intermediate in the cyanogen bromide cleavage, by
attack of the Met carbonyl oxygen on the carbon next to sulfur. If you
have a Met-Thr or Met-Ser bond, this intermediate would be further
stabilized by formation of a spirolactone due to the participation of the
side chain OH group (It's hard to explain this without drawing a picture).

Regardless of which (if either) explanation is correct, the next question
is how does CH3-SH eliminate from the peptide? Normally this only occurs
if the sulfur is first activated by conversion to a sulfonium ion (positive
charge on S), for example by treatment with cyanogen bromide or an
alkylating agent such as iodoacetamide. Has the peptide been treated with
alkylating agents? If it is a naturally occuring peptide (not synthetic),
maybe it arises from a post-translational modification of sulfur.

It's an interesting problem.

Richard Laursen
--------------------------------------------

> I would like to see if anyone has observed a modied methione which I
> may be seeing. In a recent peptide map, a new peak was observed.
>
> Analysis by protein sequencing shows very low amount of a known
> peptide sequence but with low amount a methionine (8-10 x less than
> expected) at its one site of occurrence. At that site there was no
> other peak of the height of the rest of the sequence, although there
> was a small amt of a peak at PTH-ILE and a slight increase in dmptu.
>
> MALDI MS shows the mass anticipated minus 48 daltons. Further
> fragmentation confirms the mass change to be at the site of
> methionine.
>
> Here is my question: has anyone had experience with a methionine
> degrading to dehydroamino butyric acid? Any other thoughts?
>
> Thanks for your help!
>
> Barb Root
> Bristol-Myers Squibb
> Syracuse NY

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>