Antimicrobial resistance is one of the most important threats to human, animal and plant health, and to food security [1]. Therefore, new antimicrobials are actively sought, particularly novel classes displaying a low induction of resistance, such as host-defense peptides (HDP) [2]. However, the natural HDP often present drawbacks such low in vivo stability, or high production costs. The development of short synthetic analogues with non-proteinogenic units has increased resistance to proteases, and lowered production costs [1,2]. 
The discovery of antimicrobial peptide nanodrugs can be accelerated by using site-selective modifications of customizable units in a few peptide substrates. The peptide fragments resulting from the selective modification are then attached in a combinatorial way, creating a much larger library with structural diversity, with different α-chains and N-substituents [3]. The evaluation of these libraries and the discovery of novel antimicrobial drug candidates with a promising antifungal activity will be commented herein. 

Acknowledgments: This work was financed by projects PID2020-116688RB-C21 of the Plan Estatal I + D, Ministry of Science, Spain (with European Regional Development Fund, ERDF) and project 2022CLISA40 sponsored by Fundación Caja Canarias and Fundación La Caixa. M.P. thanks Ministerio de Ciencia, Innovación y Universidades, Spain (FPU grants). 

References:
[1] (a) https://www.who.int/health-topics/antimicrobial-resistance; (b) http://www.fao.org/antimicrobial-resistance
[2] (a) Lobo, F.; González, M. S.; Boto, A.; Pérez de la Lastra, J. M. Int. J. Mol. Sci. 2023, 24, 10270. (b) Boto, A.; Pérez de la Lastra, J.; González, C. Molecules 2018, 23, 311.
[3] Hernandez, D.; Porras, M.; Boto, A. J. Org. Chem. 2023, 88, 9910.