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

Moser, Rudolf

In: Protein Engineering, Design and Selection, 1992, vol. 5, no. 4, p. 323-331

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    Title
    • Design, synthesis and structure of an amphipathic peptide with pH-inducible haemolytic activity
    Author
    • Moser, Rudolf. Biochemisches Institut der Universitãt Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Protein Engineering, Design and Selection, 1992, vol. 5, no. 4, p. 323-331. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:299534
    Summary
    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