Unexpected inhibition of S-adenosyl-L-homocysteine hydrolase by a guanosine nucleoside.
A series of shape-modified flexible nucleosides ('fleximers', 1, 2, and 3) was modeled, synthesized and subsequently assayed against S-adenosyl-L-homocysteine hydrolase (SAHase). No inhibitory activity was observed for the adenosine fleximer, which served as a substrate, but moderate inhibitory activity was exhibited by the guanosine fleximers. This is the first known report of a guanosine nucleoside analogue possessing activity against SAHase.
Seley
Katherine L
KL
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA. katherine.seley@chemistry.gatech.edu
Quirk
Stephen
S
Salim
Samer
S
Zhang
Liang
L
Hagos
Asmerom
A
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors*; D002151:Calorimetry / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006860:Hydrogen Bonding; D006868:Hydrolysis; D007288:Inosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics; D008958:Models, Molecular; D013816:Thermodynamics
D004791:Enzyme Inhibitors; D006151:Guanosine; D007288:Inosine; D043383:Adenosylhomocysteinase; D000241:Adenosine