A-Methyl-L-arginine

Thaliporphine was observed to inhibit the formation of nitrites/nitrates caused by lipopolysaccharide (LPS) in J774.2 macrophages. This inhibition was similar to that produced by cycloheximide, A -methyl-L-arginine and dexamethasone. The results of these and other studies in this report demonstrated that thaliporphine inhibited LPS induction of NO synthase expression, and that the mechanism of action of the alkaloid was via inhibition of LPS-stimulated interleukin-ip synthesis in macrophages. Pretreatment of anesthetized rats with thaliporphine... 

DDAH catalyzes the hydrolysis of A -methyl-L-arginine (12) and asymmetric A -dimethyl-L-argtnine (13) to yield L-citrulline (1) and the corresponding alkylamine (Figure 9)." " In vertebrates, two tissue-specific... 

Olken, N.M. and Marietta, M.A. (1993) A°-Methyl-L- arginine functions as an alternate substrate and mechanism-based inhibitor of nitric oxide synthase. Biochemistry, 32,9677-9685. 

K9. Kilboum, R. G., Gross, S. S., Jubran, A., Adams, J., Griffith, O. W., Levi, R., and Lodato, R. F., A,c -Methyl-L-arginine inhibits tumor necrosis factor-induced hypotension. Proc. Natl. Acad. Sci. USA. 87, 3629-3632 (1990). 

A further study by Olken and collaborators112 describes inactivation of mouse iNOS by /Vc -rncl.hyI-1.-arginine. The inactivation occurs only in the presence of oxygen. Only a small amount of 3H or 14C label from the labeled methyl group of AG-methyl-L-arginine... 

Gold, M. E., Wood, K. S., Byrns, R. E., Fulcuto, J. M., and Ignarro, L. J. (1990). N°-Methyl-L-arginine causes endothelium-dependent contraction and inhibition of cyclic GMP formation in artery and vein. Proc. Natl. Acad. Sci. U.S.A. 87, 4430-4434. 

A -Nitro-L-arginine methyl ester (L-NAME) NOS inhibition Less selective NOS inhibitor... 

The decarboxylation of diacyl peroxides was also used in the synthesis of a nonapeptide 148 and 5-methyl L-arginine 151 (Scheme 2.35) [65,66]. The peptide 148 is an analogue of an oxytocin receptor antagonist. The photolysis of precursor 146 gave 34% of product 147, which was reprotected with Fmoc and then incorporated into the oligopeptide. 5-Methyl arginine 151 was synthesized as a probe to study the nitric oxide synthase (NOS) active site and mechanism. The photolysis of 149 gave 150... 

Martin, N.I., Woodward, J.J., Beeson, W.T., and Marietta, M.A. (2007) Design and synthesis of C5 methylated L-arginine analogues as active site probes for nitric oxide synthase. Journal of the American Chemical Society, 129, 12563-12570. 

L-NAME (L-A/ -nitro-L-arginine methyl ester Af -nitro-t-arglnine methyl ester nitroarginine methyl ester) is a NITRIC OXIDE SYNTHASE INHIBITOR, extensively used as a pharmacological tool. l>NI 7-nitroindazole. 

N-a-tosyl L-arginine methyl esterase Newly generated... 

Figure 12 Proposed catalytic mechanism of DDAH. An W -methyl-L-arginine substrate is shown in blue, the core residues in black, the hydrolytic water in red, and a putative interaction with Thr165 in gray. Amino acid numbering is from Pseudomonas aeruginosa DDAH. The apo form of the enzyme is boxed.

Not only does this molecule hydrolyse the simple trypsin substrate A-tosyl-L-arginine methyl ester with kcat and Km comparable to those of the native enzyme, but it also hydro-... 

Lipopolysaccharide (20 [Ag/ml) stimulation of rat mast cells collected from the abdominal and thoracic cavities caused a significant (P <0.005) decrease in the amounts of 0 as measured by the increase in adsorbance due to the reduction of ferri-cytochrome c at 550 run (Salvemini et al. 1991). This effect of Hpopolysaccharide was in turn attenuated by treating the cells for 1 h with 300 pM 1 -monomethyl-L-arginine (P <0.0005). h/°-Mono-methyl-L-arginine alone promoted a small but significant increase in the levels of 0 (P <0.01). The release of histamine by Oj " generated by xanthine (100 [iM) xanthine oxidase (20 mU/ml) was not altered by sodium nitroprusside (80 pM). 

---