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

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 epsilon-amine groups of lysine components in four steps: I to prepare the monomer of 3-(N-epsilon-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 epsilon-amine groups of the PLA-PLL. The structure of PLA-PLL-RGD and its precursors were conformed by FTIR-Raman and H-1 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 H-1 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.