RE: Methionine oxidation, again

From: Ed Cheung (ECheung@biomira.com)
Date: Thu Mar 01 2001 - 12:57:11 EST


Vernon,

In our experience, DTT does not reduce Met(O) back to Met, however, I'm not
sure if DTT can prevent Met from being oxidized to Met(O) in air.

Ed Cheung, Ph.D.
Manager, Analytical Development
Biomira Inc.
e-mail: echeung@biomira.com <mailto:echeung@biomira.com>
Phone: 780 450-3761 ext. 148
Fax: 780 463-0871

        -----Original Message-----
        From: VERNON SHOUP [SMTP:vernon.shoup@regpha.com]
        Sent: Thursday, March 01, 2001 8:06 AM
        To: Recipients of ABRF List
        Subject: Methionine oxidation, again
        Importance: Low

        Thanks to all who responded to my question about how to get rid of
H2O2 from protein solutions, in such a way that the protein would not be
further modified. In summary, the suggestions were:

        1. Gel filtration, either with prepoured columns or by FPLC.
        2. Repeated microcentrifugal ultrafiltration (e.g. Nanosep or
Microcon)
        3. Addition of an excess of methionine.
        4. Addition of catalase (References: N. Neumann, Methods in
Enzymology, Volume XI, pp 485-487 (1967); FEBS Letters 455 247 (1999))

        DTT would probably work, but there was some uncertainty about
whether or not DTT would reduce methionine oxide in the protein. Any
comments about this?

        Now for my next question. After we isolate protein variants by
rpHPLC (C4 or C18, Acetonitrile gradients, 0.1% TFA), we dry the solutions
down by vacuum centrifugation, and then digest with trypsin for peptide
maps. Sometimes we see almost complete oxidation of the
methionine-containing peptides, but the extent of oxidition is erratic. How
does one minimize this apparent air oxidation?

        Vernon

        Vernon A. Shoup
        Regeneron Pharmaceuticals
        Rensselaer, NY 12144

        (518)488-6012
        (518)488-6030 FAX



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