Penicillin was the world’s first antibiotic used in clinical practice. After years of development, more and more antibiotics have sprung up, but the problem of drug resistance caused by the widespread use of antibiotics has gradually become prominent.
Antimicrobial peptides are considered to have broad application prospects because of their high antibacterial activity, wide antibacterial spectrum, variety, wide selection range, and low resistance mutations in target strains. At present, many antimicrobial peptides are in the clinical research stage, among which magainins(Xenopus laevis antimicrobial peptide) has entered the Ⅲ clinical trial.
Well-defined functional mechanisms
Antimicrobial peptides (amps) are basic polypeptides with a molecular weight of 20000 and have antibacterial activity. Between ~ 7000 and composed of 20 to 60 amino acid residues. Most of these active peptides have the characteristics of strong base, heat stability, and broad-spectrum antibacterial.
Based on their structure, antimicrobial peptides can be roughly divided into four categories: helical, sheet, extended, and ring. Some antimicrobial peptides consist entirely of a single helix or sheet, while others have a more complex structure.
The most common mechanism of action of antimicrobial peptides is that they have direct activity against bacterial cell membranes. In short, antimicrobial peptides disrupt the potential of bacterial membranes, alter membrane permeability, leak metabolites, and ultimately lead to bacterial death. The charged nature of antimicrobial peptides helps to improve their ability to interact with bacterial cell membranes. Most antimicrobial peptides have a net positive charge and are therefore called cationic antimicrobial peptides. The electrostatic interaction between cationic antimicrobial peptides and anionic bacterial membranes stabilizes the binding of antimicrobial peptides to bacterial membranes.
Emerging therapeutic potential
The ability of antimicrobial peptides to act through multiple mechanisms and different channels not only increases antimicrobial activity but also reduces the propensity for resistance. Acting through multiple channels, the possibility of bacteria acquiring multiple mutations at the same time can be greatly reduced, giving the antimicrobial peptides good resistance potential. In addition, because many antimicrobial peptides act on bacterial cell membrane sites, bacteria must completely redesign the structure of the cell membrane to mutate, and it takes a long time for multiple mutations to occur. It is very common in cancer chemotherapy to limit tumor resistance and drug resistance by using multiple mechanisms and different agents.
The clinical prospect is good
Develop new antimicrobial drugs to avoid the next antimicrobial crisis. A large number of antimicrobial peptides are undergoing clinical trials and show clinical potential. Much work remains to be done on antimicrobial peptides as novel antimicrobial agents. Many antimicrobial peptides in clinical trials cannot be brought to market due to poor trial design or lack of validity. Therefore, more research on the interaction of peptide-based antimicrobials with the complex human environment will be useful to assess the true potential of these drugs.
Indeed, many compounds in clinical trials have undergone some chemical modification to improve their medicinal properties. In the process, active use of advanced digital libraries and development of modeling software will further optimize the research and development of these drugs.
Although the design and development of antimicrobial peptides is a meaningful work, we must strive to limit the resistance of new antimicrobial agents. Continued development of various antimicrobial agents and antimicrobial mechanisms will help to limit the impact of antibiotic resistance. In addition, when a new antibacterial agent is put on the market, detailed monitoring and management are needed to limit the unnecessary use of antibacterial agents as much as possible.
Post time: Jul-04-2023