Design, Synthesis, and Evaluation of Acyclic <i>C-</i>Nucleoside and
<i>N</i>-Methylated Derivatives of the Ribitylaminopyrimidine
Substrate of Lumazine Synthase as Potential Enzyme Inhibitors
and Mechanistic Probes
Jinhua Chen
Thota Sambaiah
Boris Illarionov
Markus Fischer
Adelbert Bacher
Mark Cushman
10.1021/jo048975f.s001
https://acs.figshare.com/articles/dataset/Design_Synthesis_and_Evaluation_of_Acyclic_i_C_i_Nucleoside_and_i_N_i_Methylated_Derivatives_of_the_Ribitylaminopyrimidine_Substrate_of_Lumazine_Synthase_as_Potential_Enzyme_Inhibitors_and_Mechanistic_Probes/3320545
Lumazine synthase and riboflavin synthase catalyze the last two steps in the biosynthesis of
riboflavin, a vitamin that is involved in many critical biochemical reactions that are essential for
the maintenance of life. To obtain inhibitors and structural probes that could be useful in studying
the structures of bound reaction intermediates, the ribitylamino N−H moiety of the lumazine
synthase substrate was replaced by CH<sub>2</sub> and N−CH<sub>3</sub> groups. The CH<sub>2</sub> replacement unexpectedly
and completely abolished the affinity for lumazine synthase, thus revealing a critical, yet
unexplained, role of the ribitylamino N−H moiety in conferring affinity for the enzyme. In contrast,
the N−CH<sub>3</sub> replacement resulted in an inhibitor of both lumazine synthase and riboflavin synthase.
Replacement of the ribitylamino N−H moiety with epimeric C−F moieties led to inhibition of
lumazine synthase and riboflavin synthase when combined with the replacement of the 5-amino
group with a nitro substituent.
2004-10-15 00:00:00
ribitylamino
CH 2 replacement
moiety
lumazine synthase substrate
Potential Enzyme Inhibitors
lumazine synthase
riboflavin synthase catalyze
Mechanistic Probes Lumazine synthase
riboflavin synthase