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

GARRO ADRIANA; RICCI M; VEGA HISSI ESTEBAN; ADOLFO ZURITA; FÜLÖP L; BEKE-SOMFAI T; ENRIZ RD

Congreso; Biofísica en tiempos de COVID-19 : Primeras Jornadas Virtuales SAB 2020; 2020

We report atheoretical and experimental study on a new series of antibacterialpeptides with small-size. Synthesis and bioassays are reported here.In addition, different physicochemical parameters that modulateantimicrobial activity (charge, secondary structure, hydrophobicity,amphipathicity and polarity) have been evaluated. Molecular dynamicsimulations were also performed for these peptides. The biophysicalcharacterization of peptides was carried out by using differenttechniques, such as circular dichroism (CD), linear dichroism (LD),infrared spectroscopy (IR), dynamic light scattering (DLS) and TEMstudy employing model systems (liposomes) for mammalian and bacterialmembranes, respectively. Results obtained in this work allow us todraw important conclusions on two different aspects:I) Our results(theoretical and experimental) indicate that small-sized peptideshave a particular mechanism of action that is different from that oflarge peptides. These results are a support for a four-step mechanismpreviously proposed (1). It is important to remark that in thismechanism, being able to reach a threshold concentration of peptidesand thus, a non-monomeric state, is a key step for a successfulprocess. Thus, this mechanism explains the importance of maintaininga delicate balance between affinity for the bilayer surface, a lowpeptide-peptide repulsion (in order to reach the thresholdconcentration) and an acceptable tendency to penetrate into thebilayer.II) Previously, ithas been proposed as ?pharmacophore? or minimum structuralrequirement for these short peptides, a sequence with at least 3 Rand 3 W (2). Our results are in line with this proposal. An importantinformation obtained from our study is that for such 9 amino acidlong peptides, a net charge of +4 is the adequate to produceantibacterial activity. The information obtained here is veryimportant for the design of new antibacterial peptides with thesestructural characteristics.p { margin-bottom: 0.25cm; line-height: 115% }