Amiloride as a new RNA-binding scaffold with activity against HIV-1 TAR.

ABSTRACT: Diversification of RNA-targeted scaffolds offers great promise in the search for selective ligands of therapeutically relevant RNA such as HIV-1 TAR. We herein report the establishment of amiloride as a novel RNA-binding scaffold along with synthetic routes for combinatorial C(5)- and C(6)-diversification. Iterative modifications at the C(5)- and C(6)- positions yielded derivative 24, which demonstrated a 100-fold increase in activity over the parent dimethylamiloride in peptide displacement assays. NMR chemical shift mapping was performed using the 2D SOFAST- [¹H-¹³C] HMQC NMR method, which allowed for facile and rapid evaluation of binding modes for all library members. Cheminformatic analysis revealed distinct differences between selective and non-selective

SUBMITTER: Patwardhan NN 

PROVIDER: S-EPMC5546750 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature