Design, Synthesis, and Characterization of a Novel 2'-5'-Linked Amikacin-Binding Aptamer: An Experimental and MD Simulation Study.

ABSTRACT: To extend the approach of using RNA aptamers as transient protective groups for the synthesis of novel small-molecule drug derivatives from the existing aminoglycosides, we incorporated 2'-5' phosphodiester backbone modification in a structurally known neomycin RNA aptamer and studied the binding of a series of aminoglycosides using isothermal calorimetry (ITC) and molecular dynamics (MD) simulation. Experimental characterization of amikacin, a commercially available and widely used aminoglycoside for treating bacterial infections, shows that the aptamer A1 with a 2'-5' linkage between G15 and U16 exhibits a sevenfold increase in binding affinity with a lower binding energy compared to the native aptamer. Molecular dynamics (MD) simulation studies rationalize that this noncanonical linkage

SUBMITTER: Mathivanan J 

PROVIDER: S-EPMC10400016 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature