Amino Acid Composition Determines Peptide Activity Spectrum and Hot-Spot-Based Design of Merecidin

Xiuqing Wang, Biswajit Mishra, Tamara Lushnikova, Jayaram Lakshmaiah Narayana, Guangshun Wang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

There is a great interest in developing the only human cathelicidin into therapeutic molecules. The major antimicrobial region of human LL-37 corresponds to residues 17–32. The resultant peptide GF-17 shows a broad spectrum of antimicrobial activity against both Gram-positive and Gram-negative bacteria. By reducing the hydrophobic content, converting the broad-spectrum GF-17 to two narrow-spectrum peptides (GF-17d3 and KR-12) with activity against Gram-negative bacteria is successful. This study demonstrates that substitution of multiple basic amino acids by hydrophobic alanines makes a broad-spectrum peptide 17BIPHE2 (designed based on GF-17d3) active against Staphylococcal pathogens but not other bacteria tested. Taken together, the results reveal distinct charge and hydrophobic requirements for peptides to kill Gram-positive or Gram-negative bacteria. This finding is in line with the bioinformatics analysis of the peptides in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). In addition, a hot-spot arginine is identified and used to design merecidin with reduced toxicity to human cells. Merecidin protects wax moth larvae (Galleria mellonella) from the infection of methicillin-resistant Staphylococcus aureus USA300. These new selective peptides constitute interesting candidates for future development.

Original languageEnglish (US)
Article number1700259
JournalAdvanced Biosystems
Volume2
Issue number5
DOIs
StatePublished - May 2018

Fingerprint

Peptides
Amino acids
Amino Acids
Chemical analysis
Bacteria
Gram-Negative Bacteria
Basic Amino Acids
Arginine
Methicillin
Moths
Waxes
Pathogens
Bioinformatics
Methicillin-Resistant Staphylococcus aureus
Computational Biology
Alanine
Larva
Toxicity
Substitution reactions
Cells

Keywords

  • antimicrobial peptides
  • cathelicidin
  • hydrophobic content
  • peptide design

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Amino Acid Composition Determines Peptide Activity Spectrum and Hot-Spot-Based Design of Merecidin. / Wang, Xiuqing; Mishra, Biswajit; Lushnikova, Tamara; Narayana, Jayaram Lakshmaiah; Wang, Guangshun.

In: Advanced Biosystems, Vol. 2, No. 5, 1700259, 05.2018.

Research output: Contribution to journalArticle

Wang, Xiuqing ; Mishra, Biswajit ; Lushnikova, Tamara ; Narayana, Jayaram Lakshmaiah ; Wang, Guangshun. / Amino Acid Composition Determines Peptide Activity Spectrum and Hot-Spot-Based Design of Merecidin. In: Advanced Biosystems. 2018 ; Vol. 2, No. 5.
@article{ce97bb07f30944e783003999bace9a83,
title = "Amino Acid Composition Determines Peptide Activity Spectrum and Hot-Spot-Based Design of Merecidin",
abstract = "There is a great interest in developing the only human cathelicidin into therapeutic molecules. The major antimicrobial region of human LL-37 corresponds to residues 17–32. The resultant peptide GF-17 shows a broad spectrum of antimicrobial activity against both Gram-positive and Gram-negative bacteria. By reducing the hydrophobic content, converting the broad-spectrum GF-17 to two narrow-spectrum peptides (GF-17d3 and KR-12) with activity against Gram-negative bacteria is successful. This study demonstrates that substitution of multiple basic amino acids by hydrophobic alanines makes a broad-spectrum peptide 17BIPHE2 (designed based on GF-17d3) active against Staphylococcal pathogens but not other bacteria tested. Taken together, the results reveal distinct charge and hydrophobic requirements for peptides to kill Gram-positive or Gram-negative bacteria. This finding is in line with the bioinformatics analysis of the peptides in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). In addition, a hot-spot arginine is identified and used to design merecidin with reduced toxicity to human cells. Merecidin protects wax moth larvae (Galleria mellonella) from the infection of methicillin-resistant Staphylococcus aureus USA300. These new selective peptides constitute interesting candidates for future development.",
keywords = "antimicrobial peptides, cathelicidin, hydrophobic content, peptide design",
author = "Xiuqing Wang and Biswajit Mishra and Tamara Lushnikova and Narayana, {Jayaram Lakshmaiah} and Guangshun Wang",
year = "2018",
month = "5",
doi = "10.1002/adbi.201700259",
language = "English (US)",
volume = "2",
journal = "Advanced Biosystems",
issn = "2366-7478",
publisher = "Wiley-VCH Verlag",
number = "5",

}

TY - JOUR

T1 - Amino Acid Composition Determines Peptide Activity Spectrum and Hot-Spot-Based Design of Merecidin

AU - Wang, Xiuqing

AU - Mishra, Biswajit

AU - Lushnikova, Tamara

AU - Narayana, Jayaram Lakshmaiah

AU - Wang, Guangshun

PY - 2018/5

Y1 - 2018/5

N2 - There is a great interest in developing the only human cathelicidin into therapeutic molecules. The major antimicrobial region of human LL-37 corresponds to residues 17–32. The resultant peptide GF-17 shows a broad spectrum of antimicrobial activity against both Gram-positive and Gram-negative bacteria. By reducing the hydrophobic content, converting the broad-spectrum GF-17 to two narrow-spectrum peptides (GF-17d3 and KR-12) with activity against Gram-negative bacteria is successful. This study demonstrates that substitution of multiple basic amino acids by hydrophobic alanines makes a broad-spectrum peptide 17BIPHE2 (designed based on GF-17d3) active against Staphylococcal pathogens but not other bacteria tested. Taken together, the results reveal distinct charge and hydrophobic requirements for peptides to kill Gram-positive or Gram-negative bacteria. This finding is in line with the bioinformatics analysis of the peptides in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). In addition, a hot-spot arginine is identified and used to design merecidin with reduced toxicity to human cells. Merecidin protects wax moth larvae (Galleria mellonella) from the infection of methicillin-resistant Staphylococcus aureus USA300. These new selective peptides constitute interesting candidates for future development.

AB - There is a great interest in developing the only human cathelicidin into therapeutic molecules. The major antimicrobial region of human LL-37 corresponds to residues 17–32. The resultant peptide GF-17 shows a broad spectrum of antimicrobial activity against both Gram-positive and Gram-negative bacteria. By reducing the hydrophobic content, converting the broad-spectrum GF-17 to two narrow-spectrum peptides (GF-17d3 and KR-12) with activity against Gram-negative bacteria is successful. This study demonstrates that substitution of multiple basic amino acids by hydrophobic alanines makes a broad-spectrum peptide 17BIPHE2 (designed based on GF-17d3) active against Staphylococcal pathogens but not other bacteria tested. Taken together, the results reveal distinct charge and hydrophobic requirements for peptides to kill Gram-positive or Gram-negative bacteria. This finding is in line with the bioinformatics analysis of the peptides in the Antimicrobial Peptide Database (http://aps.unmc.edu/AP). In addition, a hot-spot arginine is identified and used to design merecidin with reduced toxicity to human cells. Merecidin protects wax moth larvae (Galleria mellonella) from the infection of methicillin-resistant Staphylococcus aureus USA300. These new selective peptides constitute interesting candidates for future development.

KW - antimicrobial peptides

KW - cathelicidin

KW - hydrophobic content

KW - peptide design

UR - http://www.scopus.com/inward/record.url?scp=85045324494&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045324494&partnerID=8YFLogxK

U2 - 10.1002/adbi.201700259

DO - 10.1002/adbi.201700259

M3 - Article

C2 - 30800727

AN - SCOPUS:85045324494

VL - 2

JO - Advanced Biosystems

JF - Advanced Biosystems

SN - 2366-7478

IS - 5

M1 - 1700259

ER -