• Title/Summary/Keyword: AdoHcy hydrolase

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Studies on the inhibition activities of various adenosine derivatives on S-adenosylhomocysteine hydrolase

  • Lee, Hyun-Joo;Lee, Kang-Man;Shin, Jeong-Lak
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.163.1-163.1
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    • 2003
  • The inhibitory activities of various analogues of adenosine (Group I, Group II, Group III, Group IV, Group V) were assayed by using recombinant human placental SAH hydrolase. The activity of the SAH hydrolase was determined by measuring the formation of AdoHcy from Ado and Hcy. AdoHcy was analyzed by HPLC using C18 reverse-phase column. The peak of AdoHcy was monitored at 258 nm. Among the tested compounds, fluoroneplanocin A (LJ-276) was the most potent inhibitor.

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A synthesis of sugar-modified S-adenosyl-L-homocysteine(AdoHcy) analogues as inhibitors of AdoHcy hydrolase via the coupling sugar-modified adenosine analogues with L-homocysteine sodium salt.

  • Kim, Beom-Tae;Kim, Seung-Ki;Ryu, Jeong-Hyun;Hwang, Ki-Jun
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.235.3-236
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    • 2003
  • S-adenosyl-L-homocysteine(AdoHcy) is the product of all biological methylation in which S-adenosyl-L-methionine (AdoMet) is utilized as a methyl donor and is reversibly hydrolyzed to L-homocysteine and adenosine by AdoHcy hydrolase physiologically. Inhibition of this enzyme results in intracelluar accumulation of AdoHcy leading to a feedback inhibition of AdoMet-dependent methylation reactions which are essential for viral replication. (omitted)

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Cytochrome C Release and Caspase Activation Induced by 3-Deazaadenosisne is Inhibited by Bcl-2

  • Lee Yong-Joon;Choi Mi-Hyun;Lee Jung-Hee;Kim Ho-Shik;Lee Jeong-Hwa
    • Biomedical Science Letters
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    • v.12 no.2
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    • pp.57-63
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    • 2006
  • Deazaadenosine analogs such as 3-deazaadenosine (DZA), 3-deazaaristeromycin (DZAri) and ara-3-deazaadenine (DZAra-A) were developed as inhibitors of S-adenosylhomocysteine (Ado-Hcy) hydrolase (EC 3.3.1.1). These analogs were reported to induce apoptosis in human and murine leukemic cells. But, the mechanism involved in this apoptosis was not clarified yet. In the present study, we analyze the apoptosis induced by deazaadenosine analogs in human cervival cancer cell line, HeLa and the effect of Bcl-2 on this apoptosis. Whereas neither DZAri nor DZAra-A showed inhibitory effect on HeLa cell growth, DZA induced apoptosis in HeLa cells accompanied by cytochrome c release and activation of various caspases such as caspase-2,-8,-9 and -3. In HeLa-bcl-2 cell line, a stable transfectant of HeLa cell to overexpress Bcl-2, cytochrome c release, activation of all these caspases and the resulted apoptosis by DZA were completely prevented. By in vitro assay of cytochrome c release, in addition, DZA induced cytochrome c release from purified mitochondria of HeLa-pcDNA3 cells, but not HeLa-bcl-2 cells, even in the absence of cytosolic fraction. Therefore, it can be suggested that DZA might damage directly mitochondria leading to activate intrinsic pathway of caspase and thus induce apoptosis. DZA-induced apoptosis in HeLa cells may be in a bcl-2-inhibitable manner and irrelative of Ado-Hcy hydrolase.

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A convenient synthesis of 2′ or 3′-amino-2′(or 3′)-deoxyadenosine and 5′-chloro-2′(or 3′)-amino-deoxyadenosine analogues

  • Kim, Beom-Tae;Kim, Seung-Ki;Hwang, Ki-Jun
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.365.3-366
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    • 2002
  • New and improved preparations of structurally modified nucleosides are important goals in synthetic organic chemistry because of the potential utility of these compounds as synthetic precursors of many biologically active molecules in cells. In our program to synthesize the bioactive nucleosides, such as AdoHcy hydrolase inhibitors and cyclic adenosine diphosphoribose(cADPR) analogues. (omitted)

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