Amphoteric, prevailingly cationic L-arginine polymers of poly(amidoamino acid) structure: Synthesis, acid/base properties and preliminary cytocompatibility and cell-permeating characterizations

A linear amphoteric poly(amidoamino acid), L-ARGO7, is prepared by Michael-type polyaddition of L-arginine with N,N′-methylenebisacrylamide. Chain-extension of acrylamide end-capped L-ARGO7 oligomers with piperazine leads to high-molecular-weight copolymers in which L-arginine maintains its absolute configuration. Acid/base properties of L-ARGO7 polymers show isolectric points of ≈10 and positive net average charges per repeating unit at pH = 7.4 from 0.25 to 0.40. These arginine-rich synthetic polymers possibly share some of the unique biological properties of polyarginine cell-permeating peptides. In vitro tests with mouse embryo fibroblasts balb/3T3 clone A31 show that L-ARGO7 polymers are endowed with effective cell internalization ability combined with minimal cytotoxicity. The catalyzed Michael-type polyaddition of L-arginine with N,N′-methylenebisacrylamide gives L-arginine rich amphoteric poly(amidoaminoacid)s with minimal structural variations with respect to the parent α-aminoacid. Internal buffering by the carboxyl groups limits the basicity of the guanidine groups leading to polymers with isolectric points ≈10 and 0.25-0.40 excess positive charges per unit at pH 7.4. In preliminary in vitro tests the new L-arginine rich poly(amidoaminoacid)s exhibit effective cell permeation properties combined with negligible cytotoxicity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.