Are L-adenosine and its derivatives substrates for S-adenosyl-L-homocysteine hydrolase?
Moffatt oxidation of 2',3'-O-isopropylidene-L-adenosine and treatment of the resulting crude 5'-aldehyde with hydroxylamine followed by deprotection gave L-adenosine 5'-carboxaldehyde oximes, whose enantiomers are known to be potent inhibitors of S-adenosyl-L-homocysteine (AdoHcy) hydrolase. The L-adenosine and its 5'-aldehyde oxime derivatives were found to be inactive as inhibitors of AdoHcy hydrolase. Docking calculations showed that binding of L-adenosine to AdoHcy hydrolase is weaker (higher energy) and less specific (larger number of clusters) compared to D-Ado.
Wang
Mengmeng
M
Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, USA.
Zhang
Jinsong
J
Andrei
Daniela
D
Kuczera
Krzysztof
K
Borchardt
Ronald T
RT
Wnuk
Stanislaw F
SF
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D006515:Hepatitis B virus; D008958:Models, Molecular; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013816:Thermodynamics
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D010091:Oximes; D043383:Adenosylhomocysteinase; D000241:Adenosine