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Lead optimization of antifungal peptides with 3D NMR structures analysis.

Landon C, Barbault F, Legrain M, Menin L, Guenneugues M, Schott V, Vovelle F, Dimarcq JL
Protein Sci 13 703-13 (2004)
Related entries: 1p00, 1p0a

Cited: 25 times
EuropePMC logo PMID: 14978308

Abstract

Antimicrobial peptides are key components of the innate immune response in most multicellular organisms. These molecules are considered as one of the most innovative class of anti-infective agents that have been discovered over the last two decades, and therefore, as a source of inspiration for novel drug design. Insect cystine-rich antimicrobial peptides with the CS alpha beta scaffold (an alpha-helix linked to a beta-sheet by two disulfide bridges) represent particularly attractive templates for the development of systemic agents owing to their remarkable resistance to protease degradation. We have selected heliomicin, a broad spectrum antifungal CS alpha beta peptide from Lepidoptera as the starting point of a lead optimization program based on phylogenic exploration and fine tuned mutagenesis. We report here the characterization, biological activity, and 3D structure of heliomicin improved analogs, namely the peptides ARD1, ETD-135, and ETD-151. The ARD1 peptide was initially purified from the immune hemolymph of the caterpillars of Archeoprepona demophoon. Although it differs from heliomicin by only two residues, it was found to be more active against the human pathogens Aspergillus fumigatus and Candida albicans. The peptides ETD-135 and ETD-151 were engineered by site-directed mutagenesis of ARD1 in either cationic or hydrophobic regions. ETD-135 and ETD-151 demonstrated an improved antifungal activity over the native peptides, heliomicin and ARD1. A comparative analysis of the 3D structure of the four molecules highlighted the direct impact of the modification of the amphipathic properties on the molecule potency. In addition, it allowed to characterize an optimal organization of cationic and hydrophobic regions to achieve best antifungal activity.

Articles - 1ozz mentioned but not cited (2)

  1. Lead optimization of antifungal peptides with 3D NMR structures analysis. Landon C, Barbault F, Legrain M, Menin L, Guenneugues M, Schott V, Vovelle F, Dimarcq JL. Protein Sci 13 703-713 (2004)
  2. Functional structure and antimicrobial activity of persulcatusin, an antimicrobial peptide from the hard tick Ixodes persulcatus. Miyoshi N, Saito T, Ohmura T, Kuroda K, Suita K, Ihara K, Isogai E. Parasit Vectors 9 85 (2016)


Reviews citing this publication (8)

  1. Therapeutic potential of antifungal plant and insect defensins. Thevissen K, Kristensen HH, Thomma BP, Cammue BP, François IE. Drug Discov Today 12 966-971 (2007)
  2. Structure-Activity Relationships of Insect Defensins. Koehbach J. Front Chem 5 45 (2017)
  3. Membrane-Interacting Antifungal Peptides. Struyfs C, Cammue BPA, Thevissen K. Front Cell Dev Biol 9 649875 (2021)
  4. Innate Inspiration: Antifungal Peptides and Other Immunotherapeutics From the Host Immune Response. Mercer DK, O'Neil DA. Front Immunol 11 2177 (2020)
  5. Antimicrobial Peptides with Anti-Candida Activity. Perez-Rodriguez A, Eraso E, Quindós G, Mateo E. Int J Mol Sci 23 9264 (2022)
  6. Bioactive Peptides Derived from Edible Insects: Effects on Human Health and Possible Applications in Dentistry. Ferrazzano GF, D'Ambrosio F, Caruso S, Gatto R, Caruso S. Nutrients 15 4611 (2023)
  7. Specific Focus on Antifungal Peptides against Azole Resistant Aspergillus fumigatus: Current Status, Challenges, and Future Perspectives. Pimienta DA, Cruz Mosquera FE, Palacios Velasco I, Giraldo Rodas M, Oñate-Garzón J, Liscano Y. J Fungi (Basel) 9 42 (2022)
  8. Use of Defensins to Develop Eco-Friendly Alternatives to Synthetic Fungicides to Control Phytopathogenic Fungi and Their Mycotoxins. Leannec-Rialland V, Atanasova V, Chereau S, Tonk-Rügen M, Cabezas-Cruz A, Richard-Forget F. J Fungi (Basel) 8 229 (2022)

Articles citing this publication (15)

  1. Purification and characterization of eight peptides from Galleria mellonella immune hemolymph. Cytryńska M, Mak P, Zdybicka-Barabas A, Suder P, Jakubowicz T. Peptides 28 533-546 (2007)
  2. Gene expression, antiparasitic activity, and functional evolution of the drosomycin family. Tian C, Gao B, Rodriguez Mdel C, Lanz-Mendoza H, Ma B, Zhu S. Mol Immunol 45 3909-3916 (2008)
  3. The discovery and analysis of a diverged family of novel antifungal moricin-like peptides in the wax moth Galleria mellonella. Brown SE, Howard A, Kasprzak AB, Gordon KH, East PD. Insect Biochem Mol Biol 38 201-212 (2008)
  4. Sequence structure and expression pattern of a novel anionic defensin-like gene from silkworm (Bombyx mori). Wen H, Lan X, Cheng T, He N, Shiomi K, Kajiura Z, Zhou Z, Xia Q, Xiang Z, Nakagaki M. Mol Biol Rep 36 711-716 (2009)
  5. Rational design of peptides active against the gram positive bacteria Staphylococcus aureus. Landon C, Barbault F, Legrain M, Guenneugues M, Vovelle F. Proteins 72 229-239 (2008)
  6. Identification, phylogenetic analysis and expression profile of an anionic insect defensin gene, with antibacterial activity, from bacterial-challenged cotton leafworm, Spodoptera littoralis. Seufi AM, Hafez EE, Galal FH. BMC Mol Biol 12 47 (2011)
  7. Initial insights into structure-activity relationships of avian defensins. Derache C, Meudal H, Aucagne V, Mark KJ, Cadène M, Delmas AF, Lalmanach AC, Landon C. J Biol Chem 287 7746-7755 (2012)
  8. Solution structure of a defense peptide from wheat with a 10-cysteine motif. Dubovskii PV, Vassilevski AA, Slavokhotova AA, Odintsova TI, Grishin EV, Egorov TA, Arseniev AS. Biochem Biophys Res Commun 411 14-18 (2011)
  9. Characterization and regulation of expression of an antifungal peptide from hemolymph of an insect, Manduca sexta. Al Souhail Q, Hiromasa Y, Rahnamaeian M, Giraldo MC, Takahashi D, Valent B, Vilcinskas A, Kanost MR. Dev Comp Immunol 61 258-268 (2016)
  10. Prediction of antimicrobial activity of synthetic peptides by a decision tree model. Lira F, Lira F, Perez PS, Baranauskas JA, Nozawa SR. Appl Environ Microbiol 79 3156-3159 (2013)
  11. In vitro resistance to the CSalphabeta-type antimicrobial peptide ASABF-alpha is conferred by overexpression of sigma factor sigB in Staphylococcus aureus. Zhang H, Morikawa K, Ohta T, Kato Y. J Antimicrob Chemother 55 686-691 (2005)
  12. Three-dimensional NMR structure of Hen Egg Gallin (Chicken Ovodefensin) reveals a new variation of the β-defensin fold. Hervé V, Meudal H, Labas V, Réhault-Godbert S, Gautron J, Berges M, Guyot N, Delmas AF, Nys Y, Landon C. J Biol Chem 289 7211-7220 (2014)
  13. Probing coiled-coil assembly by paramagnetic NMR spectroscopy. Zheng T, Boyle A, Robson Marsden H, Valdink D, Martelli G, Raap J, Kros A. Org Biomol Chem 13 1159-1168 (2015)
  14. Identification and Characterization of Antimicrobial Peptides From Butterflies: An Integrated Bioinformatics and Experimental Study. Wang M, Zhou Z, Li S, Zhu W, Hu X. Front Microbiol 12 720381 (2021)
  15. In silico characterization of cysteine-stabilized αβ defensins from neglected unicellular microeukaryotes. Senra MVX. BMC Microbiol 23 82 (2023)


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