S-adenosyl-L-homocysteine hydrolase

Robins, M. J., Wnuk, S. F., Mullah, K. B. and Dailey, N. K. (1994) Nucleic Acid related compounds. 80. Synthesis of 5 -5-(alkyl and aryl )-5 -(l uoro-5 -thioadenosi ncs with xenon difluoride or (diethylamido)sulfur trifluoride, hydrolysis in aqueous buffer, and inhibition of S-adenosyl-L-homocysteine hydrolase by derived adenosine 5 -aldehyde species. J. Org. Chem., 59, 544-555. 

Schowen, R. L. 2003 Biochemistry 42, 1900—1909 The catalytic strategy of S-adenosyl-L-homocysteine hydrolase Transition-state stabilization and the avoidance of abortive reactions. 

S-Adenosyl-L-methionine is the important methyl donor in biological transmethylation to form S-adenosyl-L-homocysteine, which is hydrolyzed to adenosine and homocysteine by S-adenosyl-L-homocysteine hydrolase (E.C. 3.3.1.1) in vivo. However, equilibrium of the S-adenosyl-L-homocysteine hydrolase reaction favors the direction toward synthesis of S-adenosyl-L-homocysteine. Shimizu et al. developed a simple and efficient method for the high yield preparation of S-adenosyl-L-homocysteine with S-adenosyl-L-homocysteine hydrolase of Alcaligenes faecalis, in which the cellular content of S-adenosyl-L-homocysteine hydrolase was about 2.5% of the total soluble protein. S-Adenosyl-r-homocysteine was produced at a concentration of about 80 g I. 1 with a yield of nearly 100% 661. However, when racemic... 

Figure 17-7. Structures of adenosine and related nucleosides which serve as substrates for S-adenosyl-L-homocysteine hydrolase. 1, Adenosine 2, formycin A 3, neburalin 4, adenosine Af-oxide 5, 2-chloroadenosine 6, tubercidine 7, N6-methyladenosine 8, inosine 9, 1-methyladenosine.

Using differential screening, Tanaka et al. [34] found cDNAs representing cytokinin-induced mRNAs in the tobacco thin layer system. One cDNA encodes S-adenosyl-L-homocysteine hydrolase (SAH hydrolase), which is involved in regulating intracellular transmethylation reactions. The promoter sequence of the gene was fused to the 3-glucuronidase (GUS) reporter gene and introduced in suspension-cultured cells, which rendered expression of GUS inducible by kinetin. 

S-Adenosyl-L-homocysteine hydrolase as an attractive target for antimicrobial drugs 07YZ977. 

The phosphonic aeid moiety has been shown to be inhibitors of numerous metabolic processes [99,100], In recent years, S-adenosyl-L-homocystein hydrolase(AdoHcy) has become an attractive target for drug design since its inhibitors have been shown to exhibit antiviral [101], antiparasitic [102], antiarthritic [103], and immunosuppressive effects [104], Importantly, a-aminophosphonate diesters are more attractive as intermediates for multistep synthesis than the corresponding phosphonic acids. The insolubility of the latter in both organic and neutral aqueous media complicates derivation of both the amine and acid functionalities. 

KitadeY, KojimaH, ZulfiqurF, Kim HS, WatayaY (2003) Synthesis of 2-fluoronoraristeromycin and its inhibitory activity against Plasmodium falciparum S -adenosyl-L-homocysteine hydrolase. Bioorg Med Chem Lett 13 3963-3965... 

The 5 -alkynyl(cyano) derivatives of adenosine 274 and its carbocyclic analog derivatives 231 and 232 were examined as inhibitors of S-adenosyl-L-homocysteine and S-adenosyl-L-methionine hydrolase (89EUP334361). 

Fluoronoraristeromycin (43, Fig. 1) was investigated as an inhibitor of S-adenosyl-L-homocysteine (SAH) hydrolase in Plasmodium falciparum, and showed 100-fold enhanced selectivity for toxicity to the parasite versus mammalian cells when compared to the unfluorinated noraristeromycin [67]. Analogues of SAH inhibit human DNA methyltransferases, which use S-adenosyl-L-methionine as the cofactor to transfer methyl groups to DNA [18]. The addition of a 2-fluoro substituent to SAH was found to confer selectivity for inhibition of the DNMTl isoform of enzyme over the DNMT3b2 subtype, while unfluorinated SAH was a better inhibitor of the DNMT3b2 enzyme. 

M.S. Wolfe, Y. Lee, W J. Bartlett, D.R. Borcherding, and R.T. Borchardt, 4-Modified analogues of aristeromycin and neplanocin A Synthesis and inhibitory activity toward 5-Adenosyl-L-homocysteine hydrolase, /. Med. Chem. 35 1782 (1992). 

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