Dear Neil:
Your peptide sequences are really unpleasant, so I'd like to add few
comments on the extra problems you will likely face.
At the COOH - terminal of the first sequence you also have [DS],
which is second only to [DG] in propensity towards aspartimide
formation. This [DS] will be exposed to piperidine 6 times longer than
the [DG], so that incorporation of a "backbone protected" serine
derivative, Hmb or Ser(\|/-pro), will be very helpful.
V S S D {G H <E }Y* I Y* V D P M <Q L P Y [D S] T
Fmoc-K< E P <E <E R {P T F <E Y* L <Q A }F L <E D Y
Residues shown in {}-brackets may couple with difficulties due to
probable aggregation. The related complications can be very serious in
the SPS of the second Glx-rich peptide. To minimize chain termination
via pGlu formation (indicated above with '<') we always couple residues
next to Glx as pre-formed symmetrical anhydrides. At least exclude extra
HOBt/HOAt during these couplings. It may be useful to cleave
Fmoc-protected peptide to facilitate purification from all truncated
peptides.
In case you need to obtain the second peptide in a specified
quantity, I also recommend to double the SPS scale, as a safeguard.
Good luck!
Igor Rodionov
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Laboratory of Peptide Chemistry
Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
8 Academy Avenue, Pushchino, Moscow Region
142290, Russian Federation
rodionov@fibkh.serpukhov.su
~~^~^~^~^~^~^~^~^~^~^~^~^~^~^~~
Original message from Neil Brew:
<Dear All
I have the following two Phospho-peptides to make;
V S S D G H E Y* I Y* V D P M Q L P Y D S T
K E P E E R P T F E Y* L Q A F L E D Y
Y* = Tyr(PO(OH,OBzl))-OH
Both will be made on a pioneer Fmoc synthesiser. I was going to use HATU
.49M, DIPEA 1M activators, 20% piperidine deblock. 1hr couple for all
A.A's, with Fmoc monitoring and auto extend deblock and couple. Anybody
have anything to add/suggest that would aid in these
syntheses?>
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