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

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Serra, I (Author) Other; Casu, M (Author) Other; Ceccarelli, M (Author) Other; Paula Gameiro (Author) FCUP; Rinaldi, AC (Author) Other; Scorciapino, MA (Author) Other

Journal

Title: Peptides

Vol. 105

Pages: 28-36

ISSN: 0196-9781

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00R-A8F

DOI: 10.1016/j.peptides.2018.05.010

Abstract (EN): Antimicrobial 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 a-and e-nitrogen of one lysine core. An 8-aminooctanamide was added at the C-terminus to improve membrane affinity. Its propensity for beta-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, beta-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 propensity for ordered beta-sheets. Lipid monolayers' surface pressure was measured to estimate the area/peptide and the ability to perturb lipid packing. Fluorescence spectroscopy was applied to compare peptide insertion into the lipid bilayer. Such small change in primary structure produced fundamental differences in their aggregation behavior. A regular amphipathic peptide's primary structure was responsible for ordered beta-sheets in a charge independent fashion, in contrast to unordered aggregates formed by the former analogue.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9