The membrane-active amphibian peptide caerin 1.8 inhibits fibril formation of amyloid β1-42

Yanqin Liu, Tianfang Wang, Antonio N. Calabrese, John A. Carver, Scott F. Cummins, John H. Bowie*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    5 Citations (Scopus)

    Abstract

    The amphibian host-defense peptide caerin 1.8 [1GLFKVLGSV10AKHLLPHVVP20VIAEKL(NH2)] inhibits fibril formation of amyloid β 1-42 [1DAEFRHDSG10YEVHHQKLVF20FAEDVGSNKG30AIIGLMVGGV40VIA] [Aβ42] (the major precursor of the extracellular fibrillar deposits of Alzheimer's disease). Some truncated forms of caerin 1.8 also inhibit fibril formation of Aβ42. For example, caerin 1.8 (1-13) [1GLFKVLGSV10AKHL(NH2) and caerin 1.8 (22-25) [KVLGSV10AKHLLPHVVP20VIAEKL(NH2)] show 85% and 75% respectively of the inhibition activity of the parent caerin 1.8. The synthetic peptide KLVFFKKKKKK is a known inhibitor of Aβ42 fibril formation, and was used as a standard in this study. Caerin 1.8 is the more effective fibril inhibitor. IC50 values (±15%) are caerin 1.8 (75 μM) and KLVFFKKKKKK (370 μM). MALDI mass spectrometry shows the presence of a small peak corresponding to a protonated 1:1 adduct [caerin 1.8/Aβ42]H+. Molecular dynamics simulation suggests that both hydrogen bonding and hydrophobic interactions between Aβ42 and caerin 1.8 facilitate the formation of a 1:1 complex in water. Fibril formation from Aβ42 has been proposed to be based around the 16KLVF20F region of Aβ42; this region in the 1:1 complex is partially blocked from attachment of a further molecule of Aβ42.

    Original languageEnglish
    Article number69531
    Pages (from-to)1-6
    Number of pages6
    JournalPeptides
    Volume73
    DOIs
    Publication statusPublished - 1 Nov 2015

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