Sebestyén, M., Szabó, R., Kőhidai, L. et al. Struct Chem (2017) 28: 527. doi:10.1007/s11224-016-0901-z
In this paper we report on the synthesis and solution conformation of a new set of structurally related polycationic branched chain polypeptides (poly[Lys(Xi-dl-Alam)]) with hydrophobic (Ile, Nle, Val) or cationic (Arg) amino acids at the N-terminal end of the side chains as well as their cytotoxic effect on murine bone marrow derived macrophages. Solution conformation of the polypeptides was studied with circular dichroism spectroscopy under different conditions (pH, ionic strength). The results of these comparative studies indicate that a) polypeptides could adopt an ordered (mainly helical) conformation at physiological pH and salt concentration (pH 7.4, 0.2 M NaCl); b) the nature of side chain terminal amino acid (X) could determine under which conditions the ordered structure was formed. Thus, the solution conformation of branched polypeptides could be modulated by the selection of amino acid X under physiological conditions. All polypeptides with hydrophobic amino acid at the terminal position were essentially non-toxic on macrophages, whereas the polypeptide with terminal Arg proved to be markedly cytotoxic.
polylysine based polypeptides hydrophobic side chain solution conformation in vitro cytotoxicity