RE: Peptide synthesis problems.

Liu, Chuan-Fa (cliu@amgen.com)
Mon, 5 Oct 1998 15:10:03 -0700

It appears to me that your peptide was modified by a methylene
(-CH2-) group, most likely bridging position 2 of the indole ring and
the Na atom of the Trp residue (modification at the N-ter Ser with the
formation of an oxazolidine is also a possibility, but less likely). The
methylene moiety can come from a formaldehyde derivative released during
the cleavage step from the decomposition of certain protecting groups or
simply from contaminants in the reagents/solvents used. This problem has
also been found for peptides containing N-terminal Cys residues, in
which the modification results in the formation of a relatively stable
thiazolidine. In all cases, the side product has a +12Da MW.

Solutions: Use of Fmoc-Trp(Boc)-OH for Trp incorporation in
Fmoc-based synthesis and/or addition of free cysteine as a scavenger in
the cleavage cocktail.

CF Liu
Amgen Peptide Chemistry
Boulder, CO 80301

> From: Terry Stoming
> Sent: Monday, October 5, 1998 5:00 AM
> To: Recipients of ABRF List
> Subject: Peptide synthesis problems.
>
> Item Type: Task
> Start Date: 10/05/1998 (Monday)
> Due: 10/05/1998 (Monday)
>
> We have synthesized a small 9-mer with 1-trp,3-arg,1-tyr, 1-thr,
> 1-ala. 1-ile, and an N-term ser. We did Fmoc on for the N-term serind
> and removed it later after cleavage from the resin. The calculated mw
> is 1208.39. Our mass spec (ion spray) shows a molecular ion at 1220
> with a nice 610 peak too. What in the world could have a mw
> difference of 12???
>