Warner, Katherine Deigan published the artcileValidating Fragment-Based Drug Discovery for Biological RNAs: Lead Fragments Bind and Remodel the TPP Riboswitch Specifically, Related Products of pyrazines, the publication is Chemistry & Biology (Oxford, United Kingdom) (2014), 21(5), 591-595, database is CAplus and MEDLINE.
Thiamine pyrophosphate (TPP) riboswitches regulate essential genes in bacteria by changing conformation upon binding intracellular TPP. Previous studies using fragment-based approaches identified small mol. “fragments” that bind this gene-regulatory mRNA domain. Crystallog. studies now show that, despite having micromolar Kds, four different fragments bind the TPP riboswitch site-specifically, occupying the pocket that recognizes the aminopyrimidine of TPP. Unexpectedly, the unoccupied site that would recognize the pyrophosphate of TPP rearranges into a structure distinct from that of the cognate complex. This idiosyncratic fragment-induced conformation, also characterized by small-angle X-ray scattering and chem. probing, represents a possible mechanism for adventitious ligand discrimination by the riboswitch, and suggests that off-pathway conformations of RNAs can be targeted for drug development. Our structures, together with previous screening studies, demonstrate the feasibility of fragment-based drug discovery against RNA targets.
Chemistry & Biology (Oxford, United Kingdom) published new progress about 59944-75-1. 59944-75-1 belongs to pyrazines, auxiliary class Other Aromatic Heterocyclic,Amine, name is Thieno[2,3-b]pyrazin-7-amine, and the molecular formula is C17H14F3N3O2S, Related Products of pyrazines.
Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem