Strategies to Improve the Activity and Biocompatibility: Modification of Peptide Antibiotics

As host defense peptides, peptide antibiotics exist in almost all organisms. Many of their activities come from their inactivation of bacteria, yeast, fungi, and even cancer cells. However, natural peptide antibiotics are relatively poor in stability and penetration, and have high hemolytic properties, which makes them difficult to directly apply. Therefore, natural peptide antibiotics can be modified to enhance their activity and biocompatibility. Based on the characteristics of amino acids, amino acid substitutions can be performed to study the effect of amino acid types on the activity of peptide antibiotics. The design of ultrashort peptides, cyclic peptides, and self-assembling peptides is also a way to improve the activity of peptide antibiotics. In addition, antibacterial peptides can also be conjugated with antibiotics, lipids, or metal ions to prepare antibacterial peptides with special activities. This review introduces several methods for modifying peptide antibiotics and their specific applications, providing a theoretical basis for the further application of peptide antibiotics.