Effects of amphipathic profile regularization on structural order and interaction with membrane models of two highly cationic branched peptides with β-sheet propensity

Publication date: July 2018Source: Peptides, Volume 105Author(s): Ilaria Serra, Mariano Casu, Matteo Ceccarelli, Paula Gameiro, Andrea C. Rinaldi, Mariano Andrea ScorciapinoAbstractAntimicrobial peptides attracted increasing interest in last decades due to the rising concern of multi-drug resistant pathogens. Dendrimeric peptides are branched molecules with multiple copies of one peptide functional unit bound to the central core. Compared to linear analogues, they usually show improved activity and lower susceptibility to proteases. Knowledge of structure-function relationship is fundamental to tailor their properties. This work is focused on SB056, the smallest example of dendrimeric peptide, whose amino acid sequence is WKKIRVRLSA. Two copies are bound to the α- and ε- nitrogen of one lysine core. An 8-aminooctanamide was added at the C-terminus to improve membrane affinity. Its propensity for β-type structures is also interesting, since helical peptides were already thoroughly studied. Moreover, SB056 maintains activity at physiological osmolarity, a typical limitation of natural peptides. An optimized analogue with improved performance was designed, β-SB056, which differs only in the relative position of the first two residues (KWKIRVRLSA). This produced remarkable differences. Structure order and aggregation behavior were characterized by using complementary techniques and membrane models with different negative charge. Infrared spectroscopy showed different propensi...

Source: Peptides - July 11, 2018 Category: Biochemistry Source Type: research