Development of nonfouling polypeptides with uniform alternating charges by polycondensation of the covalently bonded dimer of glutamic acid and lysine

In this work, nonfouling polypeptides with homogenous alternating charges were synthesized by polycondensation of the covalently bonded dimer of glutamic acid (E) and lysine (K) (EK dimer) with benzyloxycarbonyl (Z)-protected side chains. This facile method successfully solved the uniformity problem of nonfouling peptides caused by the copolymerization of two different monomers and enabled the incorporation of various terminal functional groups for future applications. The molecular weights (MWs) of the nonfouling peptides can be easily controlled by the ratio of the terminal group, lipoic acid, to the EK dimer. The nonfouling peptides can form self-assembling monolayers (SAMs) on a gold surface through two terminal thiol groups, which were characterized by attenuated total reflection Fourier transform infrared (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and ellipsometry (ELL). The resistance to nonspecific protein adsorption, cell attachment and bacterial adhesion of these nonfouling peptide SAMs and the in vitro cytotoxicity and haemolytic activity of these peptides were also evaluated. The results show that the lowest relative protein adsorptions of antibody (anti-IgG) and fibrinogen (Fg) on the SAMs are 5.1 ± 1.6% and 7.3 ± 1.8%, respectively, determined by enzyme-linked immunosorbent assay (ELISA), where the protein adsorption on a tissue culture polystyrene (TCPS) surface was set to 100%. Almost no obvious cell attachment and bacterial adhesion were observed, and no cytotoxicity and no haemolytic activity in vitro were detected. With the advantages of biocompatibility, biodegradability and the abundance of moieties for ligand immobilization, these nonfouling peptides developed by the facile method can be used in a wide range of biomedical applications.