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. 2023 Dec;256(4-6):317-330.
doi: 10.1007/s00232-023-00286-w. Epub 2023 Apr 25.

Peptide Flexibility and the Hydrophobic Moment are Determinants to Evaluate the Clinical Potential of Magainins

Daniel Balleza  1
Affiliations

Peptide Flexibility and the Hydrophobic Moment are Determinants to Evaluate the Clinical Potential of Magainins

Daniel Balleza. J Membr Biol. 2023 Dec.

Abstract

Using a flexibility prediction algorithm and in silico structural modeling, we have calculated the intrinsic flexibility of several magainin derivatives. In the case of magainin-2 (Mag-2) and magainin H2 (MAG-H2) we have found that MAG-2 is more flexible than its hydrophobic analog, Mag-H2. This affects the degree of bending of both peptides, with a kink around two central residues (R10, R11), whereas, in Mag-H2, W10 stiffens the peptide. Moreover, this increases the hydrophobic moment of Mag-H2, which could explain its propensity to form pores in POPC model membranes, which exhibit near-to-zero spontaneous curvatures. Likewise, the protective effect described in DOPC membranes for this peptide regarding its facilitation in pore formation would be related to the propensity of this lipid to form membranes with negative spontaneous curvature. The flexibility of another magainin analog (MSI-78) is even greater than that of Mag-2. This facilitates the peptide to present a kind of hinge around the central F12 as well as a C-terminal end prone to be disordered. Such characteristics are key to understanding the broad-spectrum antimicrobial actions exhibited by this peptide. These data reinforce the hypothesis on the determinant role of spontaneous membrane curvature, intrinsic peptide flexibility, and specific hydrophobic moment in assessing the bioactivity of membrane-active antimicrobial peptides.

Keywords: Hydrophobic moment; Intrinsic peptide flexibility; Magainins; Membrane curvature.

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References

    1. Ageitos JM, Sánchez-Pérez A, Calo-Mata P, Villa TG (2017) Antimicrobial peptides (AMPs) Ancient compounds that represent novel weapons in the fight against bacteria. Biochem Pharmacol 133:117–138. https://doi.org/10.1016/j.bcp.2016.09.018 - DOI - PubMed
    1. Aisenbrey C, Marquette A, Bechinger B (2019) The mechanisms of action of cationic antimicrobial peptides refined by novel concepts from biophysical investigations. Adv Exp Med Biol 1117:33–64. https://doi.org/10.1007/978-981-13-3588-4_4 - DOI - PubMed
    1. Amos ST, Vermeer LS, Ferguson PM, Kozlowska J, Davy M, Bui TT, Drake AF, Lorenz CD, Mason AJ (2016) Antimicrobial peptide potency is facilitated by greater conformational flexibility when binding to Gram-negative bacterial inner membranes. Sci Rep 22(6):37639. https://doi.org/10.1038/srep37639 - DOI
    1. Balleza D, Alessandrini A, Beltrán García MJ (2019) Role of lipid composition, physicochemical interactions, and membrane mechanics in the molecular actions of microbial cyclic lipopeptides. J Membr Biol 252(2–3):131–157. https://doi.org/10.1007/s00232-019-00067-4 - DOI - PubMed
    1. Balleza D, Mescola A, Alessandrini A (2020) Model lipid systems and their use to evaluate the phase state of biomembranes, their mechanical properties and the effect of non-conventional antibiotics: the case of daptomycin. Eur Biophys J 49(5):401–408. https://doi.org/10.1007/s00249-020-01445-w - DOI - PubMed

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