Synthesis and Evaluation of Oligospermines for Nucleic Acid Delivery

A variety of delivery vehicles use spermine as a polycationic component to form complexes with nucleic acids. Thus, we investigated the influence of molecular architecture, amine density, and molecular weight of oligospermines on its binding to nucleic acids. We report the synthesis of cyclic, aminocyclic and quatrefoil architecture and evaluated their efficiency to bind to nucleic acid with other linear and dendritic oligospermines synthesized in our laboratory. The effect of molecular weight was more pronounced in linear oligospermines than their cyclic counterparts. Oligospermines with similar amine density but different molecular architecture exhibited different binding profiles. Among all oligospermines evaluated, dendritic tetraspermine exhibited the highest binding affinity. Importantly, dendritic tetraspermine was less toxic than linear tetraspermine, suggesting its potential in nucleic acid delivery.