RESUMEN
We report the synthesis of two new artificial nucleobase scaffolds, 1 and 2, featuring adequate hydrogen bonding donors and acceptors for the molecular recognition of U:A and C:G base pairs, respectively. The tethering of these structures to various amino acids and the assessment of these artificial nucleobase-amino acid conjugates as RNA ligands against a model of HCV IRES IIId domain are also reported. Compound 1e displayed the highest affinity (Kd twice lower than neomycin - control). Moreover, it appears that this interaction is enthalpically and entropically favored.
Asunto(s)
Regiones no Traducidas 5'/efectos de los fármacos , Aminoácidos/farmacología , Antivirales/farmacología , Hepacivirus/efectos de los fármacos , Purinas/farmacología , Pirimidinas/farmacología , ARN Viral/metabolismo , Aminoácidos/química , Antivirales/química , Emparejamiento Base/efectos de los fármacos , Secuencia de Bases , Hepacivirus/química , Hepacivirus/metabolismo , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Ligandos , Conformación de Ácido Nucleico , Purinas/química , Pirimidinas/química , ARN Viral/químicaRESUMEN
Hevein has been found to be an essential element in coagulation of rubber particles in latex of rubber trees. In a previous study, we cloned a 1,241-bp fragment of a 5' upstream region of the hevein gene by genome walking. This fragment was analyzed by a 5' end nested deletion method in the present study, fused with a uidA (gus) gene to produce a series of tested constructs, which were transferred into C-serum of latex and the Gus activities were detected. Results showed that the fragment from -749 to -292 was sufficient for expression of gus gene in latex, and the fragment from -292 to -168 was crucial in response to abscisic acid inducement. In a transient transgenic test of rubber leaf with particle bombardment, construct Hev749 conferred gus-specific expression in veins, in which the latex tubes mainly distributed. This implies that the fragment from -749 to -292 was laticiferous-specific.