Wang, Kai-Bo; Dickerhoff, Jonathan; Wu, Guanhui; Yang, Danzhou published the artcile< PDGFR-β Promoter Forms a Vacancy G-Quadruplex that Can Be Filled in by dGMP: Solution Structure and Molecular Recognition of Guanine Metabolites and Drugs>, Safety of 7H-Purin-2-amine, the main research area is vacancy G quadruplex PDGFRbeta promoter dGMP conformation guanine drug.
Aberrant expression of PDGFR-β is associated with a number of diseases. The G-quadruplexes (G4s) formed in PDGFR-β gene promoter are transcriptional modulators and amenable to small mol. targeting. The major G4 formed in the PDGFR-β gene promoter was previously shown to have a broken G-strand. Herein, we report that the PDGFR-β gene promoter sequence forms a vacancy G-quadruplex (vG4) which can be filled in and stabilized by physiol. relevant guanine metabolites, such as dGMP, GMP, and cGMP, as well as guanine-derivative drugs. We determined the NMR structure of the dGMP-fill-in PDGFR-β vG4 in K+ solution This is the first structure of a guanine-metabolite-fill-in vG4 based on a human gene promoter sequence. Our structure and systematic anal. elucidate the contributions of Hoogsten hydrogen bonds, sugar, and phosphate moieties to the specific G-vacancy fill-in. Intriguingly, an equilibrium of 3′- and 5′-end vG4s is present in the PDGFR-β promoter sequence, and dGMP favors the 5′-end fill-in. Guanine metabolites and drugs were tested and showed a conserved selectivity for the 5′-vacancy, except for cGMP. CGMP binds both the 3′- and 5′-end vG4s and forms two fill-in G4s with similar population. Significantly, guanine metabolites are involved in many physiol. and pathol. processes in human cells; thus, our results provide a structural basis to understand their potential regulatory functions by interaction with promoter vG4s. Moreover, the NMR structure can guide rational design of ligands that target the PDGFR-β vG4.
Journal of the American Chemical Society published new progress about Drugs. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Safety of 7H-Purin-2-amine.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem