A polycation scaffold presenting tunable "click" sites: Conjugation to carbohydrate ligands and examination of hepatocyte-targeted pDNA delivery

A versatile polycation scaffold that can easily be modified with targeting ligands has been designed, synthesized, and characterized. A series of galactose-containing polymers has been produced to demonstrate the ease of modification of this polynucleotide delivery vehicle motif via the click reaction and to study how various structural modifications affect recognition by ASGPr on hepatocytes. A small library of structures was created where DCS and alkyl spacer length between the targeting group and the polymer backbone was varied. The novel polymer scaffold described proves to be a valuable tool for understanding structure/activity relationships of complexes made with receptor-targeted polymers. (Chemical Presented).