Synthesis of Components for Amphiphilic Tri-Arm Star Copolymer for Gene Delivery

Abstract

Amphiphilic block copolymers are polymers that consist of hydrophobic and hydrophilic blocks. These polymers have been of interest because of their potential use in medical applications such as gene delivery. The gene delivery vector that our group is currently synthesizing is an amphiphilic tri-arm star copolymer. The tri-arm star copolymer consists of a hydrophillic polyethylene glycol (PEG), a hydrophobic poly (lactic acid) (PLA) block, and a short cleavable oligolysine chain that will complex with DNA. In this document, model studies of lactic acid (LA) polymerization from 3-hydroxy-N-(2-methoxyethyl)-2-[(phenylmethoxy)carbonyl] propanamide (compound 1), and the synthesis of the components of the third arm; which are the cleavable disulfide compound N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) and the short oligolysine peptides chain. Model studies of LA polymerization were conducted using tin (II) octanoate as catalyst and compound (1) as the initiator for ring opening polymerization. The ring opening polymerizations were conducted in both bulk and solution; with target molecular weights ranging from 2,000 to 10,000 g/mol. The components necessary to make the third arm of the tri-arm star block copolymer are SPDP and oligolysine peptides. The synthesis of SPDP was accomplished in a two-step reaction, done according to literature. Oligolysine-rich peptides KKC and KKKC were prepared by solution phase peptide synthesis using orthogonal protecting groups