peptide synthesis

mbgbb@seqnet.dl.ac.uk
Mon, 29 Jun 1998 20:55:24 GMT

To all peptide synthesis experts,

We have synthesised a peptide with the following sequence -
N-terminus C-Y-A-S-I-N-F-Q-K-Q-P-E-D-R-Q C-terminus.(Calculated
Mw=1827.01Da)
The synthesis was performed on ABI-431A synthesiser, 0.25mM scale with FastMoc
solid phase chemistry.
Reverse phase-HPLC analysis of the peptide showed a double peak, the second
peak forming a shoulder to the major peak.
MALDI-TOF mass analysis of the two peaks showed the major HPLC peak contained a
peptide of mass m/z =1828.12. The second HPLC peak has the mass m/z = 1809.96
(with some contaminating m/z=1828.64 peak). The two peaks have a mass
difference of approximately 18 daltons.

Initially we assumed that a proportion of the serine at residue 4 may have been
converted to dehydroalanine and have tried to confirm this by Edman sequencing.
However the ratios of serine to dehydroalanine and serine to tyrosine in cycle
2 and alanine in cycle 3 on sequencing of the two peptide species appear
similar.

Does any one have an explanation how this loss of 18 daltons has occurred?

Thanks in advance

From: Sharad Mistry,
PNACL,
University of Leicester,
Lancaster Road,
Leicester, LE1 9HN, U.K.
Tel: +44 (0)116 252 5531
Fax: +44 (0)116 252 5616
Email: scm11@leicester.ac.uk

Dear Sharad,

My guess is that you have some aspartimide formation across the asp-arg.

I have made several peptides where this is the case. I don't think it is
a problem with c-terminal gln.

Graham Bloomberg
Dept. Biochemistry
Medical School
University of Bristol
Bristol BS8 1TD

g.b.bloomberg@bristol.ac.uk
+44 (0)1179-293205
Fax. +44 (0)1179-288274