Azaserine Explained

Azaserine is a naturally occurring serine derivative diazo compound with antineoplastic and antibiotic properties deriving from its action as a purinergic antagonist and structural similarity to glutamine. Azaserine acts by competitively inhibiting glutamine amidotransferase, a key enzyme responsible for glutamine metabolism.

Mechanism of Action

Azaserine inhibits the rate limiting step of the metabolic hexosamine pathway and irreversibly inhibits γ-glutamyltransferase by acting directly at the substrate-binding pocket. Independent of hexosamine pathway inhibition, azaserine has been demonstrated to protect against hyperglycemic endothelial damage by elevating serum concentrations of manganese-superoxide dismutase, directly reducing the concentration of reactive oxygen species.

Azaserine also downregulates the expression of VCAM-1 and ICAM-1 in response to TNF-α, and research indicates that it may have potential in identifying the L-leucine-favoring system transporter in human T-lymphocytes.

Properties

Azaserine has a solubility of 50 mg/mL in water, a melting point of 146-162 °C, a vapor pressure of 1.53x10⁻¹⁰mmHg at 25 °C, and decomposes before melting.

References

• Segel GB, Woodlock TJ, Murant FG, Lichtman MA . Photoinhibition of 2-amino-2-carboxybicyclo[2,2,1]heptane transport by O-diazoacetyl-L-serine. An initial step in identifying the L-system amino acid transporter . The Journal of Biological Chemistry . 264 . 28 . 16399–402 . October 1989 . 10.1016/S0021-9258(19)84720-8 . 2789219 . free .
• . Inhibition of glycosaminoglycan synthesis and protein glycosylation with WAS-406 and azaserine result in reduced islet amyloid formation in vitro . American Journal of Physiology. Cell Physiology . 293 . 5 . C1586–93 . November 2007 . 17804609 . 2365901 . 10.1152/ajpcell.00208.2007 .
• Wada K, Hiratake J, Irie M, Okada T, Yamada C, Kumagai H, Suzuki H, Fukuyama K . Crystal structures of Escherichia coli gamma-glutamyltranspeptidase in complex with azaserine and acivicin: novel mechanistic implication for inhibition by glutamine antagonists . Journal of Molecular Biology . 380 . 2 . 361–72 . July 2008 . 18555071 . 10.1016/j.jmb.2008.05.007 .
• Rajapakse AG, Ming XF, Carvas JM, Yang Z . The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects . American Journal of Physiology. Heart and Circulatory Physiology . 296 . 3 . H815–22 . March 2009 . 19136606 . 10.1152/ajpheart.00756.2008 .
• Lebedeva ZI, Kabanova EA, Berezov TT . 6-diazo-5-oxo-L-norleucine and azaserine as affinity inhibitors of glutamin(asparagin)ase . Biochemistry International . 12 . 3 . 413–20 . March 1986 . 3707592 .