Cyclodextrin-Scaffolded Alamethicin with Remarkably Efficient Membrane Permeabilizing Properties and Membrane Current Conductance

Claudia Ulrich Hjørringgaard; Brian Stougaard Vad; Vladimir Matchkov; Søren Bang Nielsen; Thomas Vosegaard; Niels Christian Nielsen; Daniel Otzen; Troels Skrydstrup

doi:10.1021/jp2098679

Cyclodextrin-Scaffolded Alamethicin with Remarkably Efficient Membrane Permeabilizing Properties and Membrane Current Conductance

Claudia Ulrich Hjørringgaard, Brian Stougaard Vad, Vladimir Matchkov, Søren Bang Nielsen, Thomas Vosegaard, Niels Christian Nielsen, Daniel Otzen, Troels Skrydstrup

Department of Chemistry - Center for Uopløselige Proteinstrukturer

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

30 Citations (Scopus)

Abstract

Bacterial resistance to classical antibiotics is a serious medical problem, which continues to grow. Small antimicrobial peptides represent a potential solution and are increasingly being developed as novel therapeutic agents. Many of these peptides owe their antibacterial activity to the formation of trans-membrane ion-channels resulting in cell lysis. However, to further develop the field of peptide antibiotics, a thorough understanding of their mechanism of action is needed. Alamethicin belongs to a class of peptides called peptaibols and represents one of these antimicrobial peptides. To examine the dynamics of assembly and to facilitate a thorough structural evaluation of the alamethicin ion-channels, we have applied click chemistry for the synthesis of templated alamethicin multimers covalently attached to cyclodextrin-scaffolds. Using oriented circular dichroism, calcein release assays, and single-channel current measurements, the α-helices of the templated multimers were demonstrated to insert into lipid bilayers forming highly efficient and remarkably stable ion-channels

Original language	English
Journal	Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical
Volume	116
Issue	26
Pages (from-to)	7652-7659
Number of pages	8
ISSN	1520-6106
DOIs	https://doi.org/10.1021/jp2098679
Publication status	Published - 5 Jul 2012

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Hjørringgaard, C. U., Vad, B. S., Matchkov, V., Nielsen, S. B., Vosegaard, T., Nielsen, N. C., Otzen, D., & Skrydstrup, T. (2012). Cyclodextrin-Scaffolded Alamethicin with Remarkably Efficient Membrane Permeabilizing Properties and Membrane Current Conductance. Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, 116(26), 7652-7659. https://doi.org/10.1021/jp2098679

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title = "Cyclodextrin-Scaffolded Alamethicin with Remarkably Efficient Membrane Permeabilizing Properties and Membrane Current Conductance",

abstract = "Bacterial resistance to classical antibiotics is a serious medical problem, which continues to grow. Small antimicrobial peptides represent a potential solution and are increasingly being developed as novel therapeutic agents. Many of these peptides owe their antibacterial activity to the formation of trans-membrane ion-channels resulting in cell lysis. However, to further develop the field of peptide antibiotics, a thorough understanding of their mechanism of action is needed. Alamethicin belongs to a class of peptides called peptaibols and represents one of these antimicrobial peptides. To examine the dynamics of assembly and to facilitate a thorough structural evaluation of the alamethicin ion-channels, we have applied click chemistry for the synthesis of templated alamethicin multimers covalently attached to cyclodextrin-scaffolds. Using oriented circular dichroism, calcein release assays, and single-channel current measurements, the α-helices of the templated multimers were demonstrated to insert into lipid bilayers forming highly efficient and remarkably stable ion-channels",

author = "Hj{\o}rringgaard, {Claudia Ulrich} and Vad, {Brian Stougaard} and Vladimir Matchkov and Nielsen, {S{\o}ren Bang} and Thomas Vosegaard and Nielsen, {Niels Christian} and Daniel Otzen and Troels Skrydstrup",

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doi = "10.1021/jp2098679",

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Hjørringgaard, CU, Vad, BS, Matchkov, V, Nielsen, SB, Vosegaard, T , Nielsen, NC , Otzen, D & Skrydstrup, T 2012, 'Cyclodextrin-Scaffolded Alamethicin with Remarkably Efficient Membrane Permeabilizing Properties and Membrane Current Conductance', Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, vol. 116, no. 26, pp. 7652-7659. https://doi.org/10.1021/jp2098679

Cyclodextrin-Scaffolded Alamethicin with Remarkably Efficient Membrane Permeabilizing Properties and Membrane Current Conductance. / Hjørringgaard, Claudia Ulrich; Vad, Brian Stougaard; Matchkov, Vladimir et al.
In: Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, Vol. 116, No. 26, 05.07.2012, p. 7652-7659.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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AU - Hjørringgaard, Claudia Ulrich

AU - Vad, Brian Stougaard

AU - Matchkov, Vladimir

AU - Nielsen, Søren Bang

AU - Vosegaard, Thomas

AU - Nielsen, Niels Christian

AU - Otzen, Daniel

AU - Skrydstrup, Troels

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N2 - Bacterial resistance to classical antibiotics is a serious medical problem, which continues to grow. Small antimicrobial peptides represent a potential solution and are increasingly being developed as novel therapeutic agents. Many of these peptides owe their antibacterial activity to the formation of trans-membrane ion-channels resulting in cell lysis. However, to further develop the field of peptide antibiotics, a thorough understanding of their mechanism of action is needed. Alamethicin belongs to a class of peptides called peptaibols and represents one of these antimicrobial peptides. To examine the dynamics of assembly and to facilitate a thorough structural evaluation of the alamethicin ion-channels, we have applied click chemistry for the synthesis of templated alamethicin multimers covalently attached to cyclodextrin-scaffolds. Using oriented circular dichroism, calcein release assays, and single-channel current measurements, the α-helices of the templated multimers were demonstrated to insert into lipid bilayers forming highly efficient and remarkably stable ion-channels

AB - Bacterial resistance to classical antibiotics is a serious medical problem, which continues to grow. Small antimicrobial peptides represent a potential solution and are increasingly being developed as novel therapeutic agents. Many of these peptides owe their antibacterial activity to the formation of trans-membrane ion-channels resulting in cell lysis. However, to further develop the field of peptide antibiotics, a thorough understanding of their mechanism of action is needed. Alamethicin belongs to a class of peptides called peptaibols and represents one of these antimicrobial peptides. To examine the dynamics of assembly and to facilitate a thorough structural evaluation of the alamethicin ion-channels, we have applied click chemistry for the synthesis of templated alamethicin multimers covalently attached to cyclodextrin-scaffolds. Using oriented circular dichroism, calcein release assays, and single-channel current measurements, the α-helices of the templated multimers were demonstrated to insert into lipid bilayers forming highly efficient and remarkably stable ion-channels

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ER -

Cyclodextrin-Scaffolded Alamethicin with Remarkably Efficient Membrane Permeabilizing Properties and Membrane Current Conductance

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