Re: Norleucine AAA

Reed Harris (reed@gene.COM)
Mon, 23 Nov 1998 13:13:20 -0800

We can analyze for norleucine in E.coli-derived recombinants using a
Beckman 6300 AAA equipped with a Beckman lithium column and buffers
Li-A & Li-D. The detector is set at 0.1 AUFS, and the column temp. is
kept at 38C to move the Tyr peak back away from norleucine.

We can quantitate down to 50 pmol Nle in a 75 microgram hydrolysate,
which usually puts us in the 0.2-0.5% Nle/Met replacement range. Most
AA peaks are off-scale, but you can get molar quantitations based on
proline.

--
Reed Harris
Genentech, Inc.
(650) 225-4187 Phone
(650) 225-3554 FAX
reed@gene.com  E-Mail

> We are working with an E.coli-produced recombinant protein (21,000 MW, 3 methionines, no cysteines) that apparently has some methionine-to-norleucine variants. One of these variants chromatographs very closely to the parent protein across a number of purification techniques: cation and anion exchange, HIC, acid rpHPLC. Does anyone have any suggestions about how to specifically enhance resolution between these species, so we can quantitate the variant without doing a peptide map? > Vernon

> Vernon A. Shoup > Regeneron Pharmaceuticals, Inc. > Rensselaer, NY 12144