Synthesis and characterization of arginine–glycine–aspartic peptides conjugated poly(lactic acid-co-l-lysine) diblock copolymer

Abstract

A biodegradable Copolymer of poly(lactic acid-co-lysine)(PLA–PLL) was synthesized by a modified method and novel Arginine–Glycine–Aspartic (RGD) peptides were chemical conjugated to the primary ε-amine groups of lysine components in four steps: I to prepare the monomer of 3-(N^ε-benzoxycarbonyl-l-lysine)-6-l-methyl-2,5-morpholinedione; II to prepare diblock copolymer poly(lactic acid-co-(Z)-l-lysine) (PLA–PLL(Z)) by ring-opening polymerization of monomer and l,l-lactide with stannous octoate as initiator; III to prepare diblock copolymer PLA–PLL by deprotected the copolymer PLA–PLL(Z) in HBr/HoAc solution; IV the reaction between RGD and the primary ε-amine groups of the PLA–PLL. The structure of PLA–PLL–RGD and its precursors were conformed by FTIR-Raman and ¹H NMR. Low weight average molecular weight (9,200 g/mol) of the PLA–PLL was obtained and its PDI is 1.33 determined by GPC. The PLA–PLL contained 2.1 mol% lysine groups as determined by ¹H NMR using the lysine protecting group’s phenyl protons. Therefore, the novel RGD-grafted diblock copolymer is expected to find application in drug carriers for tumor therapy or non-viral DNA carriers for gene therapy.