New Short Cationic Antibacterial Peptides. Synthesis, biological activity and mechanism of action

GARRO, ADRIANA; RICCI, M.; VEGA HISSI, ESTEBAN G.; ZURITA, ADOLFO; FÜLÖP, L.; BEKE-SOMFAI, T.; ENRIZ, DANIEL R.

Virtual

Congreso; Biofísica en tiempos de COVID-19; 2020

Sociedad Argentina de Biofísica

We report a theoretical and experimental study on a new series of antibacterial peptides with small-size. Synthesis and bioassays are reported here. In addition, different physicochemical parameters that modulate antimicrobial activity (charge, secondary structure, hydrophobicity, amphipathicity and polarity) have been evaluated. Molecular dynamic simulations were also performed for these peptides. The biophysical characterization of peptides was carried out by using different techniques, such as circular dichroism (CD), linear dichroism (LD), infrared spectroscopy (IR), dynamic light scattering (DLS) and TEM study employing model systems (liposomes) for mammalian and bacterial membranes, respectively. Results obtained in this work allow us to draw important conclusions on two different aspects:I) Our results (theoretical and experimental) indicate that small-sized peptides have a particular mechanism of action that is different from that of large peptides. These results are a support for a four-step mechanism previously proposed (1). It is important toremark that in this mechanism, being able to reach a threshold concentration of peptides and thus, a non-monomeric state, is a key step for a successful process. Thus, this mechanism explains the importance of maintaining a delicate balance between affinity for the bilayer surface, a low peptide-peptide repulsion (in order to reach the threshold concentration) and an acceptable tendency to penetrate into the bilayer.II) Previously, it has been proposed as ?pharmacophore? or minimum structural requirement for these short peptides, a sequence with at least 3 R and 3 W (2). Our results are in line with this proposal. An important information obtained from our study is that for such 9 amino acid long peptides, a net charge of +4 is the adequate to produce antibacterial activity. The information obtained here is very important for the design of new antibacterial peptides with these structural characteristics.