RESUMO
A small library of 1,5-triazole derivatives linking a diaminocyclopentadiol and aromatic ketones has been prepared and screened using NMR and fluorescent techniques against tRNA(Lys)(3), the HIV reverse transcription primer. The comparison of their binding properties to those of their 1,4-triazole isomers, previously discovered in a fragment-based approach, outlines the influence of the linker on affinity and binding selectivity in such an approach.
Assuntos
Infecções por HIV/tratamento farmacológico , Aminoacil-RNA de Transferência/metabolismo , RNA Viral/metabolismo , Triazóis/química , Triazóis/farmacologia , Sítios de Ligação , HIV/efeitos dos fármacos , Ligantes , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Aminoacil-RNA de Transferência/química , RNA Viral/química , Transcrição Reversa/efeitos dos fármacosRESUMO
4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for the stimulation of human iNKT cells, but this remains strongly debated. In this work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a metathesis reaction allowing sphingosine modifications from a single ethylenic alpha-galactoside precursor. The 4-deoxy-KRN7000 derivative 2, described here, induced potent cytokinic responses, comparable to those of KRN7000, both from human iNKT cells in vitro and from their murine counterpart in vivo.