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Biophysics of Proteins at Surfaces: Assembly, Activation, Signaling
Poster Abstracts
10-POS
Board 10
Amphiphilic Derivatives of Chitosan Hold Similarities with Antimicrobial Peptides in
Their Mechanism of Action
Fabio D. Nasário
1
, Marcio J. Tiera
1
, Laiz C. Silva-Gonçalves
2
, Vera A. Tiera
1
, Manoel Arcisio-
Miranda
2
,
Marcia P. Dos Santos Cabrera
1
.
1
Universidade Estadual Paulista - UNESP, São José do Rio Preto, Brazil,
2
Universidade Federal
de São Paulo - UNIFESP, São Paulo, SP, Brazil.
Chitosans have been modified and functionalized to improve their action as antimicrobials.
Antimicrobial chitosans may target the phospholipid matrix of cell membranes and this has been
considered a target towards which resistance is hardly developed. In this work two chitosan
derivatives were designed to gain hydrophobic and cationic character at different ratios. They
were synthesized and evaluated for their features as amphiphilic compounds and for their
interaction with three model membranes of different lipid composition, mimicking bacterial,
fungal and erythrocyte membranes. Antimicrobial and cytotoxic activity was also assessed,
demonstrating that both derivatives present antimicrobial activity but just the one with higher
cationic character showed cytotoxicity towards human cervical carcinoma cells. The strategy
used provided chitosan derivatives with intense lytic activity, inducing more than 70% dye
leakage and similar behavior for both derivatives in the anionic model membranes. The less
charged compound exhibits a slightly improved selectivity in relation to the anionic over the
zwitterionic bilayers. This effect indicates that it is possible to balance the
hydrophobic/hydrophilic character to improve the efficiency of chitosan derivatives. The
disturbance of the lipid acyl chain order was also observed, and together with zeta potential
measurements we hypothesize that the “charge cluster mechanism” ascribed to some
antimicrobial peptides could be applied to these chitosan derivatives.