Structure-activity study of the antibacterial peptide fallaxin

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Structure-activity study of the antibacterial peptide fallaxin. / Søndergaard, Sandra Lerche; Frimodt-Møller, Niels; Kragelund, Birthe Brandt; Hansen, Paul Robert.

I: Protein Science, Bind 16, Nr. 9, 2007, s. 1969-1976.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Søndergaard, SL, Frimodt-Møller, N, Kragelund, BB & Hansen, PR 2007, 'Structure-activity study of the antibacterial peptide fallaxin', Protein Science, bind 16, nr. 9, s. 1969-1976. https://doi.org/10.1110/ps.072966007

APA

Søndergaard, S. L., Frimodt-Møller, N., Kragelund, B. B., & Hansen, P. R. (2007). Structure-activity study of the antibacterial peptide fallaxin. Protein Science, 16(9), 1969-1976. https://doi.org/10.1110/ps.072966007

Vancouver

Søndergaard SL, Frimodt-Møller N, Kragelund BB, Hansen PR. Structure-activity study of the antibacterial peptide fallaxin. Protein Science. 2007;16(9):1969-1976. https://doi.org/10.1110/ps.072966007

Author

Søndergaard, Sandra Lerche ; Frimodt-Møller, Niels ; Kragelund, Birthe Brandt ; Hansen, Paul Robert. / Structure-activity study of the antibacterial peptide fallaxin. I: Protein Science. 2007 ; Bind 16, Nr. 9. s. 1969-1976.

Bibtex

@article{c28ada30a1c211ddb6ae000ea68e967b,
title = "Structure-activity study of the antibacterial peptide fallaxin",
abstract = "Fallaxin is a 25-mer antibacterial peptide amide, which was recently isolated from the West Indian mountain chicken frog Leptodactylus fallax. Fallaxin has been shown to inhibit the growth of several Gram-negative bacteria including Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Here, we report a structure-activity study of fallaxin based on 65 analogs, including a complete alanine scan and a full set of N- and C-terminal truncated analogs. The fallaxin analogs were tested for hemolytic activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant S. aureus, (VISA), methicillin-susceptible S. aureus (MSSA), E. coli, K. pneumoniae, and P. aeruginosa. We identified several analogs, which showed improved antibacterial activity compared to fallaxin. Our best candidate was FA12, which displayed MIC values of 3.12, 25, 25, and 50 µM against E. coli, K. pneumoniae, MSSA, and VISA, respectively. Furthermore, we correlated the antibacterial activity with various structural parameters such as charge, hydrophobicity H{"} style={"}width: 4px; height: 15px; border-width: 0px{"}/>, mean hydrophobic moment µH{"} style={"}width: 4px; height: 15px; border-width: 0px{"}/>, and -helicity. We were able to group the active and inactive analogs according to mean hydrophobicity H{"} style={"}width: 4px; height: 15px; border-width: 0px{"}/> and mean hydrophobic moment µH{"} style={"}width: 4px; height: 15px; border-width: 0px{"}/>. Far-UV CD-spectroscopy experiments on fallaxin and several analogs in buffer, in TFE, and in membrane mimetic environments (small unilamellar vesicles) indicated that a coiled-coil conformation could be an important structural trait for antibacterial activity. This study provides data that support fallaxin analogs as promising lead structures in the development of new antibacterial agents. ",
keywords = "Former LIFE faculty, alanine scan, antibacterial activity, coiled-coil conformation, fallaxin, solid-phase peptide synthesis",
author = "S{\o}ndergaard, {Sandra Lerche} and Niels Frimodt-M{\o}ller and Kragelund, {Birthe Brandt} and Hansen, {Paul Robert}",
year = "2007",
doi = "10.1110/ps.072966007",
language = "English",
volume = "16",
pages = "1969--1976",
journal = "Protein Science",
issn = "0961-8368",
publisher = "Wiley-Blackwell",
number = "9",

}

RIS

TY - JOUR

T1 - Structure-activity study of the antibacterial peptide fallaxin

AU - Søndergaard, Sandra Lerche

AU - Frimodt-Møller, Niels

AU - Kragelund, Birthe Brandt

AU - Hansen, Paul Robert

PY - 2007

Y1 - 2007

N2 - Fallaxin is a 25-mer antibacterial peptide amide, which was recently isolated from the West Indian mountain chicken frog Leptodactylus fallax. Fallaxin has been shown to inhibit the growth of several Gram-negative bacteria including Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Here, we report a structure-activity study of fallaxin based on 65 analogs, including a complete alanine scan and a full set of N- and C-terminal truncated analogs. The fallaxin analogs were tested for hemolytic activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant S. aureus, (VISA), methicillin-susceptible S. aureus (MSSA), E. coli, K. pneumoniae, and P. aeruginosa. We identified several analogs, which showed improved antibacterial activity compared to fallaxin. Our best candidate was FA12, which displayed MIC values of 3.12, 25, 25, and 50 µM against E. coli, K. pneumoniae, MSSA, and VISA, respectively. Furthermore, we correlated the antibacterial activity with various structural parameters such as charge, hydrophobicity H" style="width: 4px; height: 15px; border-width: 0px"/>, mean hydrophobic moment µH" style="width: 4px; height: 15px; border-width: 0px"/>, and -helicity. We were able to group the active and inactive analogs according to mean hydrophobicity H" style="width: 4px; height: 15px; border-width: 0px"/> and mean hydrophobic moment µH" style="width: 4px; height: 15px; border-width: 0px"/>. Far-UV CD-spectroscopy experiments on fallaxin and several analogs in buffer, in TFE, and in membrane mimetic environments (small unilamellar vesicles) indicated that a coiled-coil conformation could be an important structural trait for antibacterial activity. This study provides data that support fallaxin analogs as promising lead structures in the development of new antibacterial agents.

AB - Fallaxin is a 25-mer antibacterial peptide amide, which was recently isolated from the West Indian mountain chicken frog Leptodactylus fallax. Fallaxin has been shown to inhibit the growth of several Gram-negative bacteria including Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Here, we report a structure-activity study of fallaxin based on 65 analogs, including a complete alanine scan and a full set of N- and C-terminal truncated analogs. The fallaxin analogs were tested for hemolytic activity and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant S. aureus, (VISA), methicillin-susceptible S. aureus (MSSA), E. coli, K. pneumoniae, and P. aeruginosa. We identified several analogs, which showed improved antibacterial activity compared to fallaxin. Our best candidate was FA12, which displayed MIC values of 3.12, 25, 25, and 50 µM against E. coli, K. pneumoniae, MSSA, and VISA, respectively. Furthermore, we correlated the antibacterial activity with various structural parameters such as charge, hydrophobicity H" style="width: 4px; height: 15px; border-width: 0px"/>, mean hydrophobic moment µH" style="width: 4px; height: 15px; border-width: 0px"/>, and -helicity. We were able to group the active and inactive analogs according to mean hydrophobicity H" style="width: 4px; height: 15px; border-width: 0px"/> and mean hydrophobic moment µH" style="width: 4px; height: 15px; border-width: 0px"/>. Far-UV CD-spectroscopy experiments on fallaxin and several analogs in buffer, in TFE, and in membrane mimetic environments (small unilamellar vesicles) indicated that a coiled-coil conformation could be an important structural trait for antibacterial activity. This study provides data that support fallaxin analogs as promising lead structures in the development of new antibacterial agents.

KW - Former LIFE faculty

KW - alanine scan

KW - antibacterial activity

KW - coiled-coil conformation

KW - fallaxin

KW - solid-phase peptide synthesis

U2 - 10.1110/ps.072966007

DO - 10.1110/ps.072966007

M3 - Journal article

C2 - 17766389

VL - 16

SP - 1969

EP - 1976

JO - Protein Science

JF - Protein Science

SN - 0961-8368

IS - 9

ER -

ID: 8079246