A Structure‐Activity Investigation on Modified Analogues of an Argininocalixarene Based Non‐viral Gene Vector

The tetra-L-arginino-tetrahexyloxycalix[4]arene 1 has shown extraordinary abilities to compact and internalize different types of Nucleid Acid cargos (DNA, microRNA, PNA) into cells even known be transfected with great difficulties by commercial non-viral gene delivery systems. This activity, accompanied negligible toxicity, makes this calixarene a rather promising prototype vector for Gene Therapy. In study we report how small structural changes like i) the lower rim alkyl substituents, ii) type terminal cationic headgroups (guanidinium or primary ammonium), iii) length linker between macrocycle headgroup, iv) presence/absence basic α-amino group Arg, v) stereochemistry (L D) might affect ability novel vectors DNA deliver its cargo cells.