Design and activity study of a melittin\u2013thanatin hybrid peptide

Xiaofeng Jiang,Haixia Ge,Kun Qian,Laiyu Sun,Guangping Liu,Jingfen Li,Zhengbing Lv,Xinqiang Fang,Guoqing Zhou

doi:10.1186/s13568-019-0739-z

Xiaofeng Jiang, Haixia Ge + Show 7 more

Open Access

https://doi.org/10.1186/s13568-019-0739-z

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Abstract

The unique antimicrobial mechanism of antimicrobials make them a promising substitute for antibiotics for fighting drug-resistant bacteria. Both melittin and thanatin have antimicrobial bioactivity. However, thanatin does not inhibit the growth of Staphylococcus aureus. Melittin can inhibit S. aureus and has strong hemolytic activity. In the present study, the mutant fragments of melittin and thanatin were combined by flexible peptides to form a novel hybrid peptide, which was synthesized based on the secondary and tertiary structure prediction. The hybrid peptide inhibited S. aureus with a hemolytic concentration of above 45 μmol/L and inhibition rate in SMMC-7721 cells of 19.14%. The hybrid antimicrobial peptide, which was designed by the combination of α-helix and β-lamellar antimicrobial peptides, showed that both types of peptides did not interact with each either on spatial structure or biological activities, thereby providing a novel idea for the design of artificial antimicrobial peptides.

Highlights

The antimicrobial functions of traditional antibiotics are achieved by destroying the bacterial cell wall or blocking the biosynthesis of substances required for the biological activity of bacteria (Goossens et al 2005; Mangoni and Bhunia 2016)
Physicochemical properties and structure prediction of polypeptides Physicochemical properties of the hybrid peptide The isoelectric point and molecular weight of the designed hybrid peptide are shown in Table 1 (Fehlbaum et al 1996)
Secondary structure prediction by the HNN method The secondary structure of the modified C-terminal amino acids of melittin based on the HNN method are as follows: DSC ccchhhhhhhhhccc MLRC ceeeeeeeeeeeeec PHD ccceceehhhhhhhc Sec.Cons. ccce?eehhhhh??c The predicted secondary structure of thanatin is as follows: DSC cccccceeeeecccccccccc MLRC ccccceeeeeeeccccccccc PHD ccccccceeeecccccccccc Sec.Cons. cccccceeeeecccccccccc The predicted secondary structure of the hybrid peptide is as follows: DSC cccchhhhhhhhhhcccccccccceeeeecccccccccc MLRC ccchhhhhhhhhhhcccccccccceeeeeeccccccccc PHD cceeeeeehhhhhhhcccccccceeeeeeeccccccccc Sec.Cons. ccc?hhhhhhhhhhcccccccccceeeeeeccccccccc

Summary

Introduction

The antimicrobial functions of traditional antibiotics are achieved by destroying the bacterial cell wall or blocking the biosynthesis of substances required for the biological activity of bacteria (Goossens et al 2005; Mangoni and Bhunia 2016). Known mechanisms of action include the destruction of cell membranes, interference with nucleic acid and protein synthesis, the inhibition of cell wall synthesis, and interference with cell division (Bolintineanu et al 2012; Lee and Park 2014; Ursic-Bedoya et al 2011; Lee et al 2016; Fabbretti et al 2012; Malmsten 2014; Cho et al 2012; Xia et al 2018). With a primary structure of GSKKPVPIIYCNRRTGKCQRM, is a type of antimicrobial peptide consisting of 21 amino acid residues. It is found in the insect Podisus maculiventris. Despite its broad-spectrum antimicrobial properties, it does not inhibit S. aureus (Fehlbaum et al 1996; Mandard et al 1998)

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