## 4 Conclusions  
CAMPs are widely recognized as some of the most attractive solutions to the antibiotic resistance problem, in fact, their peculiar mechanism of action makes a rapid insurgence of resistant strains more unlikely [3; 4; 5; 6; 7]. Until now, however, it has been difficult to translate CAMPs into clinical practice due to some relevant drawbacks; first of all, their sensitivity to proteases results in short in vivo half-lives and limited administration routes. Furthermore, the high costs of producing CAMPs would prevent industrial scale-up. We designed the peptoid P13#1 to attempt to overcome these two issues. The peculiar structures of peptoids make them intrinsically resistant to proteases, and the sub-monomer method makes their production easier and cheaper production. Moreover, we chose to use only residues without stereogenic centers and groups that might have made the synthesis more complex, increased production costs and reduced yields. We designed P13#1 to mimic the general structural and functional features of CAMPs and of vertebrate cathelicidins without aiming to reproduce a specific CAMP. Nonetheless, it shows similarities with some of the shortest natural cathelicidins, as discussed in Section 2.1. As anticipated, P13#1 shows biological activities similar or even better than those of the reference CAMPs. It shows bactericidal and wide-spectrum antimicrobial activities similar to cathelicidins and cryptic cathelicidin-like peptides, a greater antibiofilm activity than that of LL-37 and an ability to neutralize the proinflammatory activities of LPSs which is comparable to the activity of colistin. The characterization of the labeled versions has also shown that at the molecular level, P13#1 has a behavior which is very similar to that of a cryptic cathelicidin-like CAMP. In an air pouch model of subcutaneous infection with _S. aureus_, P13#1 showed antimicrobial and anti-inflammatory activities comparable to those of ampicillin and gentamicin. Although additional experiments must be performed to evaluate its in vivo efficacy in different models of infection and routes of administration, P13#1 can be considered a potential antimicrobial peridomimetic candidate for therapeutic applications. **Supplementary Materials:** The following supporting information can be downloaded at: [[https://www.mdpi.com/article/10.3390/ph16101386/s1](https://www.mdpi.com/article/10.3390/ph16101386/s1)]([https://www.mdpi.com/article/10.3390/ph16101386/s1](https://www.mdpi.com/article/10.3390/ph16101386/s1)), Figure S1: Representative Monte-Carlo-minimized structures of P13#1 using water solvation; Figure S2: Comparison between representative Monte-Carlo-minimized structures of P13#1 using octanol solvation and the NMR structures of bovine indolicidin; Figure S3: Structure and fluorescence properties of the labeled peptoids and peptides; Figure S4: Time variations in the emission spectra after excitation at 330 nm of Luc-GKY20 and Luc-P13#1 in the presence of bacterial cells; Figure S5: Time variations in the emission spectra of aLuc-GKY20 and aLuc-P13#1 in the presence of bacterial cells; Figure S6: Viability of Raw 264.7 murine macrophage cells treated with P13#1; Figure S7: Effects of (P)GKY20 and P13#1 on the release of TNF\(\alpha\) from human THP-1 cells treated with LPS from _P. aeruginosa_ 10; Figure S8: HPLC analysis of P13#1; Figure S9: HPLC analysis of CG-P13#1. **Author Contributions:** Conceptualization, M.M. and E.N. ; methodology, V.C., A.B., I.I., F.D.R., E.C., E.P., M.M. and E.N. ; formal analysis, V.C., A.B., I.D.N., E.C. and E.N. ; investigation, V.C., A.B., I.D.N., A.D., I.I., M.S., R.C., N.D., E.C., A.T., E.P. and E.N. ; writing--original draft preparation, V.C., A.B., I.I. and E.N. ; writing--review and editing, V.C., A.B., I.I., F.D.R., E.C., E.P., M.M. and E.N. ; supervision, E.N. ; project administration, E.N. ; funding acquisition, I.I., F.D.R. and E.N. ; All authors have read and agreed to the published version of the manuscript.