You are right. You will have difficulty coupling to p-nitroaniline.
And secondly, it is most likely that you will epimerize the peptide that you
are activating at the COOH-terminal-residue.
There is no efficient way to do your coupling as far as I know.
An alternative would be to synthesize you peptide starting at the second
residue, take it off of the resin, and then couple it to the amino acid
nitroanilide. But, your peptide would have to be N-alpha protected before
doing the coupling.
Or, you build up your peptide minus the last residue on an oxime resin, then
aminolye it off using your amino acid nitroanilide.
Your target molecule is not simple/straightworward to get to.
Good luck. NLB
At 07:52 PM 98/7/22 -0600, you wrote:
>hello,
>
>thank you for your reply, it was much appreciated. it turns out now,
>the customer has decided the p-nitroanilide should be on the c-terminus
>so i will cleave the peptide, activate the cooh with hatu/nmm and then
>add p-nitro aniline to form an amide bond. i am worried, however, that
>the nh2 will be too deactivated by the p-no2 group to be very reactive.
>have you had any experience with adding this group? things would be so
>much simpler if i could talk him into the side chain version so i could
>just buy the stuff :-)
>
>jane
>
>****************************************************
>*Jane Nagel MSc (Med Chem), BSc Pharm *
>*BioTools Inc. Laboratory Services *
>*E-mail: jane@biotools.com *
>*Mobile phone:403-906-0284 *
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>****************************************************
>
>
N. Leo Benoiton
Department of Biochemistry
University of Ottawa
Ottawa, Ontario, Canada K1H 8M5
Tel: 613 562 5800, Ext. 8216
Fax: 613 562 5440
eMail: benoiton@uottawa.ca