| |
Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 32, Number 1, January/February,
pp.86-91
A Gas Chromatographic–Mass Spectrometric
Approach to Examining Stereoselective Interaction of Human
Plasma Proteins with Soman
David T. Yeung[1,2], J. Richard Smith[3],
Richard E. Sweeney[4], David E. Lenz[1], and Douglas M. Cerasoli[1],
[1]Physiology and Immunology Branch, Research Division, U.S.
Army Medical Research Institute of Chemical Defense, 3100 Ricketts
Point Road, Aberdeen Proving Ground, Maryland 21010-5400;
[2]Department
of Pharmacology and Experimental Therapeutics, University of
Maryland at Baltimore, 655 W. Baltimore Street, Baltimore,
Maryland 21201;
[3]Medical Diagnostic and Chemical Branch, Analytical
Toxicology Division, U.S. Army Medical Research Institute of
Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving
Ground, Maryland 21010-5400; and
[4]RESECO Research Engineering
Consultants, P.O. Box 554, Nottingham, Pennsylvania 19362
The organophosphorus (OP) nerve agent soman (GD)
contains two chiral centers (a carbon and a phosphorus atom),
resulting in four stereoisomers (C+P+, C–P+, C+P–,
and C–P–); the P– isomers exhibit a mammalian
toxicity that is ~1000-fold greater than that of the P+ isomers.
The capacity to assess the binding or hydrolysis of each of the
four stereoisomers is an important tool in the development of
enzymes with the potential to protect against GD intoxication.
Using a gas chromatography–mass spectrometry-based approach,
we have examined the capacity of plasma- derived human serum
albumin, plasma-purified human butyrylcholinesterase, goat milk-derived
recombinant human butyrylcholinesterase, and recombinant human
paraoxonase 1 to interact with each of the four stereoisomers
of GD in vitro at pH 7.4 and 25°C. Under these experimental
conditions, the butyrylcholinesterase samples were found to bind
GD with a relative preference for the more toxic stereoisomers
(C–P– > C+P– > C–P+ > C+P+),
while human serum albumin and paraoxonase 1 interacted with GD
with a relative preference for the less toxic isomers (C–P+/C+P+ > C+P–/C–P–).
The results indicate that these human proteins exhibit distinct
stereoselective interactions with GD. The approach described
presents a means to rapidly assess substrate stereospecificity,
supporting future efforts to develop more effective OP bioscavenger
proteins.
Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
This
article is available in its entirety by fax for $40.00 each.
Visa, MasterCard and AMEX accepted.
To
order electronically click here
or call: 847-647-2900 ext. 1323
or fax request to: 847-647-1155.
To order multiple copies click here.
Please indicate JAT
volume and issue along with page numbers. |
|
Home | Subscribe
| Current Issue | Back Issues
| Search | Advertise | Other Publications
| |
