33147-25-0Relevant articles and documents
New 7-methylguanine derivatives targeting the influenza polymerase PB2 cap-binding domain
Pautus, Stéphane,Sehr, Peter,Lewis, Joe,Fortuné, Antoine,Wolkerstorfer, Andrea,Szolar, Oliver,Guilligay, Delphine,Lunardi, Thomas,Décout, Jean-Luc,Cusack, Stephen
, p. 8915 - 8930 (2013)
The heterotrimeric influenza virus polymerase performs replication and transcription of viral RNA in the nucleus of infected cells. Transcription by "cap-snatching" requires that host-cell pre-mRNAs are bound via their 5′ cap to the PB2 subunit. Thus, the PB2 cap-binding site is potentially a good target for new antiviral drugs that will directly inhibit viral replication. Docking studies using the structure of the PB2 cap-binding domain suggested that 7-alkylguanine derivatives substituted at position N-9 and N-2 could be good candidates. Four series of 7,9-di- and 2,7,9-trialkyl guanine derivatives were synthesized and evaluated by an AlphaScreen assay in competition with a biotinylated cap analogue. Three synthesized compounds display potent in vitro activity with IC50 values lower than 10 μM. High-resolution X-ray structures of three inhibitors in complex with the H5N1 PB2 cap-binding domain confirmed the binding mode and provide detailed information for further compound optimization.
Synthesis and some spectroscopic properties of porphyrin derivatives connected with nucleobases (adenine, thymine, guanine and cytosine) by alkanamide chains
Hisatome, Masao,Maruyama, Noriaki,Ikeda, Koichi,Furutera, Tetsuo,Ishikawa, Tomiyasu,Yamakawa, Koji
, p. 1801 - 1811 (2007/10/03)
Several kinds of porphyrin derivatives covalently connected with adenine, thymine, guanine, cytosine or adenine-thymine pair in a stacking mode between the porphyrin and nucleobase moiety have been synthesized via amide formation reaction of (2-aminophenyl)porphyrin derivatives with nucleobase-alkanoic acids, and characterized by spectroscopic methods. In the 1H-NMR spectra of these nucleobase-porphyrins the proton signals of the nucleobase moieties appear at remarkably higher fields than those of the reference compounds (the corresponding nucleobase-alkanoates) which have no porphyrin moiety. The behaviors of the high field shifts, due to the diamagnetic ring current effect of the porphyrin ring, reflect the characteristic conformational features of these compounds in which the base moieties are located at the upper zone of the porphyrin ring. The Soret bands of the porphyrin in the electronic absorption spectra were markedly weaker in intensity compared with those of the reference compound which has no nucleobase moiety. Both the high-field shifts of the base protons and the hypochromic effects on the Soret band are larger in guanine and cytosine systems than those in adenine and thymine systems, respectively. Those results indicate greater affinity of guanine and cytosine for porphyrin in comparison with adenine and cytosine, respectively, and this conclusion is compatible with the reported electronic spectral properties of mixtures of polynucleotides and water-soluble porphyrin derivatives.
