Synthesis and biological evaluation of novel neamine-nucleoside conjugates potentially targeting to RNAs

Eighteen novel neamine-nucleoside conjugates with ethylenediamine-lysine or ethylenediamine-arginine as the linker were synthesized and their potential binding to A site of 16S RNA and TAR RNA was evaluated using SPR (surface plasmon resonance). Compared with neamine, compounds 10i and 10q show 6.3 and 4.8 times potential in binding to A site of 16S RNA and eight and six times potential in binding to TAR RNA, respectively. According to the data of SPR, it indicates that amino acid residue and nucleobase moieties of the designed neamine-nucleosides conjugates exhibit the important contributions for the binding to A site of 16S RNA and TAR RNA. The molecular docking study on the interaction between the ligands and A site of 16S RNA is in agreement with the experimental data. The novel type of modification may provide a promising way for the development of neamine derivatives effectively targeting to RNAs.

A new class of neamine-nucleoside conjugates, in which an ethylenediamine-amino acid were used as linker for the modification of the 5-hydroxyl group of neamine by nucleosides, was synthesized. The interactions between these compounds 10a-r with the A site of 16S RNA and TAR RNA were evaluated by dissociation constants (KD values in μM) using SPR method.