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l-Methionine sulfoximine

Names
IUPAC name (2S)-2-Amino-4-(S-methylsulfonimidoyl)butanoic acid
Other names l-Methionine sulfoximine; MSO
Identifiers
CAS Number	15985-39-4
3D model (JSmol)	Interactive image
Beilstein Reference	1725509
ChEBI	CHEBI:28490
ChemSpider	80339
ECHA InfoCard	100.016.224
EC Number	217-845-8
PubChem CID	89034
UNII	M9P6YZ6JX9
CompTox Dashboard (EPA)	DTXSID201031266
InChI InChI=1S/C5H12N2O3S/c1-11(7,10)3-2-4(6)5(8)9/h4,7H,2-3,6H2,1H3,(H,8,9)/t4-,11?/m0/s1Key: SXTAYKAGBXMACB-DPVSGNNYSA-N
SMILES CS(=N)(=O)CC(C(=O)O)N
Properties
Chemical formula	C5H12N2O3S
Molar mass	180.22 g·mol
Related compounds
Related compounds	Buthionine sulfoximine Glufosinate
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references

Methionine sulfoximine (MSO, also known as MetSox) is an irreversible glutamine synthetase inhibitor. It is the sulfoximine derivative of methionine with convulsant effects.

Methionine sulfoximine is composed of two different diastereomers, which are L-S-Methionine sulfoximine and L-R-Methionine sulfoximine. These affect the longevity of the model mouse for Lou Gehrig's disease. Overproduction of glutamate results to excitotoxicity, which kills the cell. Since methionine sulfoximine inhibits glutamate production in the brain, it prevents excitotoxicity. Thus, increasing the longevity of the mice.

Mechanism of action

MSO is phosphorylated by glutamine synthetase. The resulting product acts as a transition state analog that is unable to diffuse from the active site, thereby inhibiting the enzyme.

References

1. Carroll, P.; Waddell, S. J.; Butcher, P. D.; Parish, T. (2011). "Methionine sulfoximine resistance in Mycobacterium tuberculosis is due to a single nucleotide deletion resulting in increased expression of the major glutamine synthetase, GlnA1". Microbial Drug Resistance. 17 (3): 351–355. doi:10.1089/mdr.2010.0125. PMC 3161625. PMID 21875360.
2. Rowe, WB; Meister, A (June 1970). "Identification of L-methionine-S-sulfoximine as the convulsant isomer of methionine sulfoximine". Proceedings of the National Academy of Sciences of the United States of America. 66 (2): 500–6. Bibcode:1970PNAS...66..500R. doi:10.1073/pnas.66.2.500. PMC 283073. PMID 4393740.
3. Brusilow, William S. A. (2017-04-24). "Identification of the isomer of methionine sulfoximine that extends the lifespan of the SOD1 G93A mouse". Neuroscience Letters. 647: 165–167. doi:10.1016/j.neulet.2017.03.029. ISSN 0304-3940. PMID 28323087. S2CID 45664203.
4. Bame, Monica; Pentiak, Patricia A.; Needleman, Richard; Brusilow, William S. A. (2012-12-01). "Effect of Sex on Lifespan, Disease Progression, and the Response to Methionine Sulfoximine in the SOD1 G93A Mouse Model for ALS". Gender Medicine. 9 (6): 524–535. doi:10.1016/j.genm.2012.10.014. ISSN 1550-8579. PMID 23217569.
5. Krajewski, W. W.; Jones, T. A.; Mowbray, S. L. (18 July 2005). "Structure of Mycobacterium tuberculosis glutamine synthetase in complex with a transition-state mimic provides functional insights". Proceedings of the National Academy of Sciences. 102 (30): 10499–10504. Bibcode:2005PNAS..10210499K. doi:10.1073/pnas.0502248102. PMC 1180770. PMID 16027359.

• Convulsants
• Glutamine synthetase inhibitors
• Alpha-Amino acids
• Amino acid derivatives
• Sulfoximines