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3074349 
Journal Article 
Facile and Quantitative Synthesis of a Poly(ethylene glycol)-b-Poly(l-arginine) Block Copolymer and Its Use for the Preparation of Polyion Complex Micelles with Polyanions for Biomedical Applications 
Kudo, S; Nagasaki, Y 
2015 
1 
Macromolecular Rapid Communications
ISSN: 1022-1336
EISSN: 1521-3927 
36 
21 
1916-1922 
English 
26218495 
WOS:000364340800009 
Though l-arginine-containing polymers show versatile biological functions, a precisely controlled synthesis of poly(ethylene glycol)-b-poly(l-arginine) (PEG-b-PArg) block copolymers has not been reported. Here, an effective method for the synthesis of PEG-b-PArg block copolymers is developed. In order to obtain PEG-b-PArg, a two-step reaction, i.e., synthesis of PEG-b-poly(l-ornithine) is employed, followed by guanidinylation with N,N'-bis(tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine. This procedure quantitatively converts amino groups to guanidium groups at the side chains of peptide segments under mild conditions. Polyion complex (PIC) micelles are prepared by mixing the positively charged PEG-b-PArg with negatively charged homo-polyelectrolytes such as hyaluronic acid (HA) or chondroitin sulfate C (CS). PIC micelles prepared with CS show a higher stability than those prepared with HA, probably due to strong interactions between guanidium cations in PEG-b-PArg and carboxylate/sulfate in CS. Thus, PIC micelles containing PArg are a potentially effective arginine carrier for the development of in vivo therapeutic applications for various diseases related to nitric oxide, which is generated from inducible nitric oxide synthase in macrophages using l-arginine as a substrate. 
alpha-amino acid N-carboxyanhydride (NCA); guanidinylation; poly(ethylene glycol) (PEG); polyion complex micelle (PIC micelle); poly-L-arginine