A Novel Mechanism-based Inhibitor (6′-Bromo-5′,6′-didehydro-6′-deoxy-6′-fluorohomoadenosine) That Covalently Modifies Human Placental S-Adenosylhomocysteine Hydrolase
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چکیده
منابع مشابه
(E)-5',6'-didehydro-6'-deoxy-6'-fluorohomoadenosine: a substrate that measures the hydrolytic activity of S-adenosylhomocysteine hydrolase.
(E)-5',6'-Didehydro-6'-deoxy-6'-fluorohomoadenosine (EDDFHA), which is a poor substrate for the oxidative activity of S-adenosyl-L-homocysteine (AdoHcy) hydrolase and thus a poor mechanism-based inhibitor was shown to be a good substrate for the hydrolytic activity of this enzyme. Incubation of EDDFHA with AdoHcy hydrolase (NAD+ form) produces a large molar excess of hydrolytic products [e.g., ...
متن کاملMechanism of inactivation of S-adenosylhomocysteine hydrolase by (E)-5',6'-didehydro-6'-deoxy-6'-halohomoadenosines.
S-Adenosylhomocysteine (AdoHcy) hydrolase is irreversibly inactivated by (E)-5',6'-didehydro-6'-deoxy-6'-halohomoadenosines (EDDHHAs, halogen = I, Br, and Cl). The inactivation is concomitant with the reduction of the enzyme-bound NAD+ (E.NAD+) to NADH, the release of halide ion, and the formation of adenine (Ade) from the EDDHHAs. The mechanism of this inactivation involves two catalytic pathw...
متن کاملMechanisms of inactivation of human S-adenosylhomocysteine hydrolase by 5',5',6',6'-tetradehydro-6'-deoxy-6'-halohomoadenosines.
In an effort to design more specific and potent inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase, we investigated the mechanisms by which 5',5',6', 6'-tetradehydro-6'-deoxy-6'-halohomoadenosines (X = Cl, Br, I) inactivated this enzyme. The 6'-chloro (a) and 6'-bromo (b) acetylenic nucleoside analogues produced partial ( approximately 50%) loss of enzyme activity with a concomitant ( appr...
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Treatment of a protected 9-(5, 6-dideoxy-beta-D-ribo-hex-5-ynofuranosyl)adenine derivative with silver nitrate and N-iodosuccinimide (NIS) and deprotection gave the 6'-iodo acetylenic nucleoside analogue 3c. Halogenation of 3-O-benzoyl-5,6-dideoxy-1, 2-O-isopropylidene-alpha-D-ribo-hex-5-enofuranose gave 6-halo acetylenic sugars that were converted to anomeric 1,2-di-O-acetyl derivatives and co...
متن کاملPreparation of 6-azafulleroid-6-deoxy-2,3-di-O-myristoylcellulose.
6-Azafulleroid-6-deoxy-2,3-di-O-myristoylcellulose (3) was synthesized from 6-azido-6-deoxycellulose (1) by two reaction steps. The myristoylation of compound 1 with myristoyl chloride/pyridine proceeded smoothly to give 6-azido-6-deoxy-2,3-di-O-myristoylcellulose (2) in 97.0% yield. The reaction of compound 2 with fullerene (C(60)) was carried out by microwave heating to afford compound 3 in h...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 1998
ISSN: 0021-9258
DOI: 10.1074/jbc.273.29.18191