Identification and functional characterisation of Esculentin-2 HYba peptides and their C-terminally amidated analogs from the skin secretion of an endemic frog

Abstract

Here, we report the identification, functional characterization and the effect of C-terminal amidation on the activity profile of two novel esculentin-2 peptides (esculentin-2 HYba1 and esculentin-2 HYba2). The parent peptides and their analogs exhibited potent activity against the tested gram positive and negative bacteria. The effect of amidation was evident in the activity profile of fish pathogens and killing kinetics. The analogs showed a tenfold decrease in MIC and the killing time was reduced to 10-15 minutes. The hemolytic potential was unaltered upon amidation. The selectivity index revealed that these peptides are more selective to bacteria than mammalian cells. Cytotoxicity against Hep3B cells reveals their potential to destroy cancer cells; they showed potential inhibition compared to anticancer drug silymarin. The study also highlights the need for further truncations and modifications of esculentin peptides for developing them as lead drug molecules.

A Comprehensive Review of Patented Antimicrobial Peptides from Amphibian Anurans

“…Based on a review of the scientific literature, patent-related anuran AMPs have a broad spectrum of antibacterial and antifungal activities. Remarkably, some peptides such as B1CTcu2, B1CTcu3, B1CTcu4, , brevinin-1JDc, DMS-PS1, DMS-PS2, esculentin-2 HYba1, esculentin-2 HYba2, , ranalexin, temporin-1Ga, and temporin-SHf have shown activity against MRSA strains. It is essential to highlight that some of these peptides, such as buforin I and II and dermaseptin-S4 showed activity against Candida neoformans , whereas B1CTcu5 stands out for its antituberculosis (anti-TB) activity (Supporting Information 1.5), , which are priority pathogens according to the WHO’s agenda for antimicrobial resistance in human health…”

Enhancing activity of food protein‐derived peptides: An overview of pretreatment, preparation, and modification methods

“…Amidation modification involves the conversion of the C‐terminal carboxylic acid group (–COOH) of a peptide to an amide group (–CONH 2 ), which can be achieved through the use of amidation agents such as carbodiimides or enzymatic catalysis using peptidylglycine α‐amidating monooxygenase(PAM) or other amidating enzymes (Carlson et al., 2015; Cui et al., 2013; De et al., 2006) (Figure 4d). This modification is commonly found in natural peptides and has been extensively studied (Vineeth Kumar et al., 2021). The amidation reaction requires the C‐terminal Gly residue of the peptide substrate, and peptides ending with other amino acids cannot be amidated (Kulathila et al., 1998).…”

“…Amidation modification has numerous biomedical applications, including the treatment of neurological dysfunction (Bousquet‐Moore et al., 2010), sleep apnea (Kuyama et al., 2009), cancer, hypertension (Dennison et al., 2009), and other disorders (Vineeth Kumar et al., 2021). Additionally, amidation can increase the cationic activity of antimicrobial peptides, making them useful against bacterial infections.…”

“…Additionally, amidation can increase the cationic activity of antimicrobial peptides, making them useful against bacterial infections. Amidation can also improve the stability of peptide secondary structures such as α‐helix and β‐sheet by preventing degradation by proteases and enhancing resistance to thermal and chemical denaturation (Vineeth Kumar et al., 2021; Zhu et al., 2021).…”

Engineering Approaches for the Development of Antimicrobial Peptide-Based Antibiotics

“…The C-terminal amidation of the Mac1 peptide also plays an important role in maintaining a stable α-helical structure in contact with micelles and results in higher antibacterial activity [ 42 ]. Upon amidation, esculentin-2 peptide analogs showed increased antimicrobial activity and selectivity [ 43 ]. Moreover, AMPs can be modified in the N-terminus and C-terminus at the same time.…”