Abstract
The poor stability of antibacterial peptide to protease limits its clinical application. Among these limitations, trypsin mainly exists in digestive tract, which is an insurmountable obstacle to orally delivered peptides. OM19R is a random curly polyproline cationic antimicrobial peptide, which has high antibacterial activity against some gram-negative bacteria, but its stability against pancreatin is poor. According to the structure-activity relationship of OM19R, all cationic amino acid residues (l-arginine and l-lysine) at the trypsin cleavage sites were replaced with corresponding d-amino acid residues to obtain the designed peptide OM19D, which not only maintained its antibacterial activity but also enhanced the stability of trypsin. Proceeding high concentrations of trypsin and long-time (such as 10 mg/mL, 8 h) treatment, it still had high antibacterial activity (MIC = 16–32 µg/mL). In addition, OM19D also showed high stability to serum, plasma and other environmental factors. It is similar to its parent peptide in secondary structure and mechanism of action. Therefore, this strategy is beneficial to improve the protease stability of antibacterial peptides.
Highlights
In recent decades, bacterial resistance has become more and more serious due to the abuse of antibiotics [1,2]
We have done related research and found that OM19D does not destroy the integrity of cells and does not affect the permeability of the cell membrane, which is similar to the parent peptide
The results showed that OM19D had a significant effect on intracellular protein concentration, and the protein concentration decreased significantly with the increase of time and concentration
Summary
Bacterial resistance has become more and more serious due to the abuse of antibiotics [1,2]. There are a variety of proteases in organisms, such as trypsin, which can lead to the degradation and inactivation of antimicrobial peptides. These proteases are one of the barriers preventing the clinical application of antimicrobial peptides [6,8]. Some newly designed and discovered antimicrobial peptides have been studied on protease resistance, most of them were only studied for the stability and hydrolysis rate of antimicrobial peptides at low concentrations of protease (e.g., 0.1 mg/mL) [9,10]. Wang et al designed an antimicrobial peptide resistant to high concentrations of protease and carried out related research [11]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
