Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection
Silvana Alfei , Sara Castellaro and Gaby Brice Taptue
Dipartimento di Farmacia (DIFAR), Università di Genova, Viale Cembrano,4 16148-I, Genova, Italia
Abstract: Dendrimers, the emerging man made, highly branched, star-shaped macromolecules with nanometer-scale dimensions are well known for their well defined and high controlled architecture, their versatility and high functionality and are of eminent interest in nanomedical applications such as drug delivery, gene transfection, and imaging. In this paper, versatile protocols for the synthesis of polyester-based, hydrolysable, polycationic dendrimers have been setup. A fourth generation dendrimer equipped with 48 peripheral hydroxyl groups was prepared from 2,2-bis(hydroxymethyl)propanoic acid and was used for grafting BOC-amino acids or as “hypercores” on which dendrons functionalized with BOC-amino acids were attached. A library of 15 polycationic homo- and hetero-dendrimers in the form of hydrochloride was obtained. Their structures and composition were confirmed by NMR analysis and by experimental molecular weight computed by volumetric titration. Their buffer capacity and results obtained from cytotoxicity assays and tests of binding with both pDNA and siRNA were very satisfactory.
Keywords : Polyester-based polycationic dendrimers; 2, 2-bis(hydroxymethyl)propanoic acid ; amino acids; p DNA and siRNA binding ; buffer capacity. ©2017 ACG Publication. All right reserved.