N-terminal Myristoylation Enhanced the Antimicrobial Activity of Antimicrobial Peptide PMAP-36PW

Abstract

Drug-resistant bacteria infections and drug residues have been increasing and causing antibiotic resistance and public health threats worldwide. Antimicrobial peptides (AMPs) are novel antimicrobial drugs with the potential to solve these problems. Here, a peptide based on our previously studied peptide PMAP-36PW was designed via N-terminal myristoylation and referred to as Myr-36PW. The fatty acid modification provided the as-prepared peptide with good stability and higher antimicrobial activity compared with PMAP-36PW in vitro. Moreover, Myr-36PW exhibited effective anti-biofilm activity against Gram-negative bacteria and may kill bacteria by improving the permeability of their membranes. In addition, the designed peptide Myr-36PW could inhibit the bacterial growth of Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa GIM 1.551 to target organs, decrease the inflammatory damage, show an impressive therapeutic effect on mouse pneumonia and peritonitis experiments, and promote abscess reduction and wound healing in infected mice. These results reveal that Myr-36PW is a promising antimicrobial agent against bacterial infections.

Advances in the stability challenges of bioactive peptides and improvement strategies

“… Chemical modification D-amino acid substitution IRIKIRIK Mao et al (2021) Polybia-CP Jia et al (2017) A20FMDV2 Cardle et al (2021) KRLFKKLLKYLRKF Lu et al (2020) Unnatural amino acid substitution Afamelanotide Chia (2021) Bivalirudin Cyclosporine Pasireotide Increase molecular mass Endostatin-derived peptide Zhou et al (2009) RKDVY Tan et al (2017) . Cyclization Cyclized opioid peptide Piekielna et al (2013) Tachyplesin peptides Vernen et al (2019) N/C-terminal modification or substitution Antimicrobial peptide Li et al (2021) PMAP-36PW Liu et al (2020) RLYE Yun et al (2019) A20FMDV2 Hung et al (2017) Encapsulation Microcapsules Antimicrobial oyster peptides Zhang et al (2009) Phaseolus lunatus L . peptides Cian et al (2019) α-helical polypeptide Morikawa et al (2005) Insulin Aiedeh et al (1997) Liposome Antioxidant peptide Ramezanzade et al (2021) RLSFNP Zhang et al (2019) Insulin Cui et al (2015) …”

Porcine Myeloid Antimicrobial Peptides: A Review of the Activity and Latest Advances

“…aureus ATCC 25923 and P. aeruginosa GIM1.551, Myr-36PW showed a prominent therapeutic effect on mouse pneumonia and peritonitis experiments compared with those of PMAP-36PW, and it promoted abscess reduction and wound healing in infected mice. Compared to the penicillin antibiotic, there was no significant difference in the therapeutic effect (47). This study provides an important reference value for the development of novel antimicrobial drugs.…”

“…In recent years, our group has performed research on the structural modification and antimicrobial activity of PMAPs. According to the structure and mechanism of PMAPs, many scholars have designed multiple novel modified peptides with increased stability and antimicrobial activity (43)(44)(45)(46)(47)(48)(49)(50). This review mainly summarizes the research progress on the structural characteristics and biological activities of PMAPs in recent years.…”

“…PMAP-36 is a highly cationic amphiphilic α-helical antimicrobial peptide consisting of 36 amino acid residues with a molecular weight of 4157.22 Da (47,59), and the complete amino acid sequence of PMAP-36 is GRFRRLRKKTRKRLKK IGKVLKWIPPIVGSIPLGCG (59). PMAP-36 has the highest net charge with 13 positively charged amino acids (seven lysines and six arginines).…”

Antimicrobial Peptides: From Design to Clinical Application

“…N-terminal myristoylation via conjugating myristic acid to porcine myeloid antimicrobial peptide-36 (PMAP-36) analog PMAP-36PW can improve their permeabilization activity on Gram-negative bacteria and anti-biofilm activity [114]. N-terminal cholesterol-modified peptide PMAP-37(F34-R) improved antibacterial activity against S. aureus, displaying antibiofilm activity and high stability in different pH conditions, as well as resistance to salt, serum, and boiling [115].…”