Synthesis of R-(TREN-DBP)

piper-idine, N,N-dimethylformamide (DMF), N,N-diisopro-pylethylamine (DIPEA) : from Sigma-Aldrich. N-hydroxybenzotriazole (HOBt), and 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetra-methyluronium (HBTU) were purchased from Anas-pec (San Jose, CA) and Fmoc-l-Arg(pbf)-OH was from Novabiochem (San Diego, CA).

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Amino acid coupling to the PAMAM was performed in anhydrous DMF for 4 h at room temperature with 4 equivalents of HOBt, HBTU, Fmoc-Arg(pbf)-OH and 7.3 equiv. of DIPEA, respectively. The product was precipitated in ethyl ether and washed with excess ether. The Fmoc groups of Fmoc-Arg(pbf)-coupled dendrimer was removed by adding 30% piperidine in DMF (v/v). After 1 h of deprotection reaction, the mixture was precipitated in ethyl ether and washed with excess ether. The reagent (95:2.5:2.5, trifluoroacetic acid/triisopropylsilane/
H 2 O, v/v) was used for deprotection of pbf groups of arginine (6 h at room temperature) and the final product was precipitated in ethyl ether and washed with excess ether. The product was solubilized in water and dialyzed against pure water at 4 8C for overnight. Then, the product was collected after freeze-drying yielding white powder.