One of the main advantages in the use of antimicrobial peptides in antibiotic therapy is the reduced chance of resistance development, since these peptides target the cell membrane phospholipid matrix. Mechanisms of the selective action found in some bioactive peptides are investigated as a means to orient structural optimizations that can enhance the therapeutic action and at the same time minimizing toxic or undesirable side effects. Moreover studies carried out in model membranes have evidenced that features of the lipid composition of bilayers are important for selectivity and to our understanding of facts derived from this interaction. Chitosans and some of its cationic derivatives similarly modify the characteristics of lipid bilayers through mechanisms much less known and studied. This project intends to synthesize a series of new molecules, which are conjugates of antimicrobial and/or tumoricidal peptides and modified chitosans, looking forward to increased efficiency in the biological activity and to lower toxicity. Since peptides, chitosans and other anphiphilic molecules exert activity on the phospholipid matrix through mechanisms, which are not well understood, studies of the interaction of these conjugated molecules with the lipid bilayer will be carried out to evaluate the relationship composition/structure/activity on model cell membranes. Additionally cytotoxicity and biological activity experiments in vitro will be performed to help selecting the best conjugated molecules for future evaluation in vivo. (AU)
Articles published in Agência FAPESP Newsletter about the research grant:
LAURENTI, JULIANA BERGAMASCO;
RIBEIRO POVINELLI, ANA PAULA;
DE GODOY, MOACIR FERNANDES;
BRAILE, DOMINGO MARCOLINO;
FLORES DA ROCHA, TANIA R.;
D' AMICO, ELBIO ANTONIO;
NERY, JOSE GERALDO.
Enhanced pro-coagulant hemostatic agents based on nanometric zeolites.
Microporous and Mesoporous Materials,
Web of Science Citations: 6.