###### Abstract
In this regard, it is particularly interesting to note that polymyxins, natural CAMPs that are widely used as topical and systemic antibiotics [22], contain several modified amino acids, protected chain termini and a cyclic structure which confer resistance to proteolysis. In order to fully exploit the pharmacological potential of CAMPs, an intriguing strategy is to develop antimicrobial peptidomimetics which are able to structurally and functionally mimic CAMPs but are resistant to proteases. Several peptidominetic have been used to develop CAMP mimics [23], and peptoids are among the most promising [24]. Peptoids, oligomers of \(N\)-substituted glycines, are regionisomers of peptides characterized by the fact that the side chains are shifted from the \(\alpha\)-carbon to the nitrogen atom of the polyamide backbone. This feature makes peptoids resistant to endogenous proteases [25]. Moreover, the straightforward synthesis of peptoids (based on the solid-phase \"sub-monomer\" approach in which no protective groups are required) expedites their preparation (in linear and cyclic forms) [24] and justifies their use as anti-infective agents. In peptoids, the presence of substituents on the nitrogen atom of the amide backbone hampers the formation of \(\alpha\)-helices or strands, which are typically present in peptides. Additionally, peptoids can form polyproline helices I and II so that structured amphipathic frames can be designed and modelled in silico via molecular dynamics or Monte Carlo methods [26]. Most designed antimicrobial peptoids were inspired by helical CAMPs which, in the presence of lipids, can adopt an amphipathic helical structure responsible for their strong interaction with bacterial membranes [27]. As the peptoid backbone is devoid of stereogenic centers, peptoids can form helical structures with defined helicity only if they contain a large proportion of chiral aromatic side chains, such as those present in \(N\)-(\(S\))- and \(N\)-(\(R\))-(\(1\)-phenylethylly)-glycine (\(N\)spe and \(N\)rpe) or similar residues. In fact, most designed peptoids were based on a three-residue repeat, (B-A-A)\({}_{n}\), in which B is a basic residue and A is a hydrophobic residue, usually a chiral aromatic residue, e.g., \(N\)spe or \(N\)rpe [27; 28; 29; 30]. Peptoids containing only \(N\)spe residues fold as right-handed helices similar to polyproline I helix (with all the peptide bonds in the _cis_ configuration and three residues per turn), whereas peptoids containing only \(N\)rpe fold as left-handed helices [27; 31]. However, more recent studies have demonstrated that helicity and defined chirality are not essential prerequisites for a high level of antimicrobial activity, while a reduced degree of helicitydecreases toxicity, thus improving the pharmacological index [32]. These findings are not completely unexpected as many highly active CAMPs are not helical and some have no regular secondary structure, even when bound to membranes (e.g., indolicidin and tritrpticin [33]). Moreover, the stability of several CAMPs was improved by changing one or more L-amino acids into a D-amino acid [13; 34; 35]. Even if these changes often significantly alter the secondary structure, antimicrobial activity is generally retained or even improved [34; 35; 36; 37]. Here, we describe the biological properties of P13#1, a designed 13-residue peptoid comprising only achiral monomers, with broad-spectrum bactericidal activity and an LPS-scavenging activity comparable to that of polymysin E (also known as colistin), a lipopeptide with strong and specific binding to LPSs [22]. Moreover, an antibiofilm activity greater than that of LL-37, the only human cathelicidin [38], was observed for P13#1. Finally, P13#1 was highly effective in vivo in a mouse model of subcutaneous infection in which it showed neglectable toxicity.