IMHO:
You aren't clear about your stoichiometry regarding activator. Remember
(This is a lesson learned the hard way): Excesses of uronium activators will
cap off your nucleophilic amine. (Meth. Enzym.,289,124). You could be
trying so hard to activate your carboxylate and not washing out excess
activator, your incoming amine doesn't stand a chance.
Also, I had a similar coupling (On-resin i-i+4 cyclization) which ONLY
worked with TFFH (Advanced Chem Tech) activation. Could help in your
circumstance.
David H. Singleton
Scientist
Pfizer Central Research
PO Box 8118-101
Eastern Point Road
Groton, CT 06340
-----Original Message-----
From: dvenug@nybc.org [mailto:dvenug@nybc.org]
Sent: Tuesday, February 08, 2000 1:01 PM
To: Recipients of ABRF List
Subject: Side chain modification
Hello all,
I have been trying to attach a mono protected diamine
{Trt-NH-(CH2)4-NH2.AcOH} to the side chain (COOH) of a Glu (23 AA long
peptide attached to the resin) by standard Fmoc coupling protocols. I
tried HOBT / HBTU and HOAT / HATU protocols using 10 fold excess of the
mono protected diamine for varying amounts of time. The reaction proceeded
to a certain extent, since I could see the adduct in the MALDI spectrum.
However, the required adduct was present only up to a maximum of 8 % as
evidenced by HPLC and MALDI results.
Now, my questions are
1. Is there anybody who tried to do this reverse order coupling (i.e. COOH
on the resin and amine in the solution using FMOC chemistry) and what are
the findings ?
2. What is the best source of information available on this particular
subject (I did a reasonable search in the literature)
thank you all for the attention
D. Venugopal
MicroChemistry
LFKRI/NYBC
New York 10021
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