Synthesis of arginine-decorated amphipilic dendrimers

Dendrimers are macromolecules characterized by well defined molecular structures, narrow polydispersity index, generally high solubility and stability. Cationic dendrimers for their capacity of electrostatically binding genetic materials to form nanosized complexes find applications as non-viral vectors to deliver the genetic material into target cells in order to correct genetic defects (gene therapy). Since polycation systems are often toxic and show moderate transfection ability, chemical modifications aimed at introducing molecular moieties able to reduce these drawbacks are required. In this respect the arginine moiety appears particularly appealing since it is known that dendrimers containing arginine are known to improve siRNA cellular uptake1 and efficiency of transfection.2 The presence of hydrophobic segments in the dendrimer structure is also important in the internalization process.3 In this communication we report synthesis and NMR characterization of new polycation polyester-based dendrimers modified both at the core with a C-18 saturated alkyl chain and at the periphery by introducing arginine or arginine and lysine residues. The presented multistep syntheses exploit 2-hydroxymethyl-2-methyl-1,3-propanediol as the core molecule and 2,2-bis(hydroxymethyl)propanoic acid as the building block to create the polyester backbone. 1) LIU, X.; LIU, C.; ZHOU, J.; CHEN, C.; QU, F.; ROSSI, J. J.; ROCCHI, P.; PENG L. Nanoscale 2015, 7, 3867-3875. 2) KIM, T.; BAI, C. Z.; NAM, K.; PARK, J. J. Control. Release 2009, 136, 132-139. 3) WANG, F.; WANG, Y.; WANG, H.; SHAO, N.; CHEN, Y.; CHENG, Y. Biomaterials 2014, 35, 9187-9198.