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Design, synthesis and structure of an amphipathic peptide with pH-inducible haemolytic activity


Moser, Rudolf (1992). Design, synthesis and structure of an amphipathic peptide with pH-inducible haemolytic activity. Protein Engineering, Design & Selection, 5(4):323-331.

Abstract

A synthetic, 26-residue peptide having a strong helix forming potential in the protonated state was designed to interact with lipid bilayers in a pH-dependent way. On the basis of this concept a cluster of four glutamk acid residues was inserted in the central region of the amphipathic peptide to promote helix destabilization by mutual charge repulsion at neutral pH. Protonation of these residues might then bring about both a pH-mediated change in hydrophobteity and conformation forming a membrane-active amphiphilk helix. The sequence GLGTLLTLLEFLLEELLEFLKRKRQQamide produced by the design strategy induced pH-triggered lysis of human erythrocytes. A molecular model correlating the lytic activity to the formation of transmembrane pores which were detected by electron microscopy in erythrocyte membranes is discussed. Circular dichroism studies indicated a selfassociation of the monomeric random coil form with increasing peptide concentration leading to the apparent induction of strong a-helix formation (˜ 100% helkity) in the fully aggregated state. However, no pH-dependent helixrandom coil transition was observed, implying that interhelical hydrophobk and ionic interactions not only govern the self-association but also decisively influence the conformational stability of the peptide

Abstract

A synthetic, 26-residue peptide having a strong helix forming potential in the protonated state was designed to interact with lipid bilayers in a pH-dependent way. On the basis of this concept a cluster of four glutamk acid residues was inserted in the central region of the amphipathic peptide to promote helix destabilization by mutual charge repulsion at neutral pH. Protonation of these residues might then bring about both a pH-mediated change in hydrophobteity and conformation forming a membrane-active amphiphilk helix. The sequence GLGTLLTLLEFLLEELLEFLKRKRQQamide produced by the design strategy induced pH-triggered lysis of human erythrocytes. A molecular model correlating the lytic activity to the formation of transmembrane pores which were detected by electron microscopy in erythrocyte membranes is discussed. Circular dichroism studies indicated a selfassociation of the monomeric random coil form with increasing peptide concentration leading to the apparent induction of strong a-helix formation (˜ 100% helkity) in the fully aggregated state. However, no pH-dependent helixrandom coil transition was observed, implying that interhelical hydrophobk and ionic interactions not only govern the self-association but also decisively influence the conformational stability of the peptide

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > Biotechnology
Physical Sciences > Bioengineering
Life Sciences > Biochemistry
Life Sciences > Molecular Biology
Language:English
Date:1 January 1992
Deposited On:16 Oct 2018 14:20
Last Modified:31 Jul 2020 02:14
Publisher:Oxford University Press
ISSN:1741-0126
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/protein/5.4.323
Related URLs:https://www.swissbib.ch/Search/Results?lookfor=nationallicenceoxford101093protein54323 (Library Catalogue)

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