The natural, peptaibolic peptide SPF-5506-A4 adopts a β-bend spiral structure, shows low hemolytic activity and targets membranes through formation of large pores

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The natural, peptaibolic peptide SPF-5506-A4 adopts a β-bend spiral structure, shows low hemolytic activity and targets membranes through formation of large pores. / Frahm, Heidi; Hansen, Sara K; Vad, Brian S; Nielsen, Erik H; Nielsen, Jakob T; Vosegaard, Thomas; Skrydstrup, Troels; Otzen, Daniel E.

I: B B A - Proteins and Proteomics, Bind 1854, Nr. 8, 08.2015, s. 882-889.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{7d492742c9734b0989e601dee0191ecd,
title = "The natural, peptaibolic peptide SPF-5506-A4 adopts a β-bend spiral structure, shows low hemolytic activity and targets membranes through formation of large pores",
abstract = "The medium-length fungal peptaibol SPF-5506-A4 has been shown to inhibit formation of the Aβ peptide involved in Alzheimer''s disease. As Aβ is a cleavage-product from the membrane-bound APP protein, we hypothesized that SPF-5506-A4's activity might be linked to membrane interactions in general. Here we describe the synthesis, structure and membrane interactions of SPF-5506-A4. The challenging synthesis was carried out on solid phase and a detailed conformational analysis in solution revealed a β-bend ribbon spiral core structure with flexible termini. Investigations of its membrane activity revealed low hemolytic activity, limited inhibition of both Gram-positive and Gram-negative cell growth and a preference for an overall negatively charged membrane surface mimicking the bacterial cell surface. SPF-5506-A4 is the first peptaibol to be shown to facilitate leakage of large (4.6nm diameter) fluorescence-labeled dextran from vesicles while leaving the vesicles intact. We conclude that SPF-5506-A4 follows the toroidal pore model in its mode of action.",
author = "Heidi Frahm and Hansen, {Sara K} and Vad, {Brian S} and Nielsen, {Erik H} and Nielsen, {Jakob T} and Thomas Vosegaard and Troels Skrydstrup and Otzen, {Daniel E}",
note = "Copyright {\circledC} 2015 Elsevier B.V. All rights reserved.",
year = "2015",
month = "8",
doi = "10.1016/j.bbapap.2015.03.003",
language = "English",
volume = "1854",
pages = "882--889",
journal = "B B A - Proteins and Proteomics",
issn = "1570-9639",
publisher = "Elsevier BV",
number = "8",

}

RIS

TY - JOUR

T1 - The natural, peptaibolic peptide SPF-5506-A4 adopts a β-bend spiral structure, shows low hemolytic activity and targets membranes through formation of large pores

AU - Frahm, Heidi

AU - Hansen, Sara K

AU - Vad, Brian S

AU - Nielsen, Erik H

AU - Nielsen, Jakob T

AU - Vosegaard, Thomas

AU - Skrydstrup, Troels

AU - Otzen, Daniel E

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2015/8

Y1 - 2015/8

N2 - The medium-length fungal peptaibol SPF-5506-A4 has been shown to inhibit formation of the Aβ peptide involved in Alzheimer''s disease. As Aβ is a cleavage-product from the membrane-bound APP protein, we hypothesized that SPF-5506-A4's activity might be linked to membrane interactions in general. Here we describe the synthesis, structure and membrane interactions of SPF-5506-A4. The challenging synthesis was carried out on solid phase and a detailed conformational analysis in solution revealed a β-bend ribbon spiral core structure with flexible termini. Investigations of its membrane activity revealed low hemolytic activity, limited inhibition of both Gram-positive and Gram-negative cell growth and a preference for an overall negatively charged membrane surface mimicking the bacterial cell surface. SPF-5506-A4 is the first peptaibol to be shown to facilitate leakage of large (4.6nm diameter) fluorescence-labeled dextran from vesicles while leaving the vesicles intact. We conclude that SPF-5506-A4 follows the toroidal pore model in its mode of action.

AB - The medium-length fungal peptaibol SPF-5506-A4 has been shown to inhibit formation of the Aβ peptide involved in Alzheimer''s disease. As Aβ is a cleavage-product from the membrane-bound APP protein, we hypothesized that SPF-5506-A4's activity might be linked to membrane interactions in general. Here we describe the synthesis, structure and membrane interactions of SPF-5506-A4. The challenging synthesis was carried out on solid phase and a detailed conformational analysis in solution revealed a β-bend ribbon spiral core structure with flexible termini. Investigations of its membrane activity revealed low hemolytic activity, limited inhibition of both Gram-positive and Gram-negative cell growth and a preference for an overall negatively charged membrane surface mimicking the bacterial cell surface. SPF-5506-A4 is the first peptaibol to be shown to facilitate leakage of large (4.6nm diameter) fluorescence-labeled dextran from vesicles while leaving the vesicles intact. We conclude that SPF-5506-A4 follows the toroidal pore model in its mode of action.

U2 - 10.1016/j.bbapap.2015.03.003

DO - 10.1016/j.bbapap.2015.03.003

M3 - Journal article

C2 - 25796141

VL - 1854

SP - 882

EP - 889

JO - B B A - Proteins and Proteomics

JF - B B A - Proteins and Proteomics

SN - 1570-9639

IS - 8

ER -