RE: Isoelectric peptide purification

Breslav, Michael [PRI] (MBreslav@prius.jnj.com)
Thu, 18 Mar 1999 18:52:26 -0500

Henry,
The best way to remove TFA is to use an ion-exchange resin. I did not use
any additional ammonium acetate or HCl, but dilute acetic acid. The
resulting peptide then is in the acetate form. Please, note that ammonium
trifluoroacetate is not volatile enough to be removed by lyophilisation.
However, it is worth to check if this peptide precipitates in a zwitterion
form if TFA is neutralized with NH4OH.
Regards,
Michael Breslav
R.W.Johnson PRI
Spring House, PA

> ----------
> From: Henry Keutmann[SMTP:keutmann@helix.mgh.harvard.edu]
> Sent: Thursday, March 18, 1999 5:32 PM
> To: Recipients of ABRF List
> Subject: Isoelectric peptide purification
>
> To my ABRF colleagues:
> A collaborator has a question regarding the purification of a
> tripeptide at or near its isoelectric point. He purified it by HPLC and
> wants to eliminate all residual TFA, isolating and lyophilizing it at its
> isoelectric point of about 5.3. We should be able to replace the TFA with
> ammonium acetate (perhaps with an intermediate treatment with dilute HCl)
> for ion-exchange (e.g. mono-S) chromatography.
> Firstly, will this effectively remove residual TFA?
> Second, after lyophilization what will be the state of the peptide
> in terms of salt content: will acetate and ammonium remain as counterions
> at the N and C terminus, or is there a way in which they can be removed
> (e.g. replaced by water, or preferably retrieved as the noncomplexed
> peptide)? Would the salt form be detectable on mass spec?
> Thanks for any advice!
> Henry Keutmann
>
> Endocrine Unit, Wellman 501
> Mass. General Hospital
> Boston MA 02114
> 617-726-3966
>
>