Solution structures of stomoxyn and spinigerin, two insect antimicrobial peptides with an α-helical conformation

Céline Landon; Hervé Meudal; Nathalie Boulanger; Philippe Bulet; Françoise Vovelle

doi:10.1002/bip.20370

Linking sequence patterns and functionality of alpha-helical antimicrobial peptides

Bioinformatics ◽

10.1093/bioinformatics/bty1048 ◽

2018 ◽

Vol 35 (16) ◽

pp. 2713-2717 ◽

Cited By ~ 2

Author(s):

Igor E Eliseev ◽

Ivan N Terterov ◽

Anna N Yudenko ◽

Olga V Shamova

Keyword(s):

Antimicrobial Peptides ◽

Rational Design ◽

Therapeutic Potential ◽

Deep Understanding ◽

Supplementary Information ◽

Helical Conformation ◽

Efficient Design ◽

Sequence Patterns ◽

Functional Features ◽

Natural Peptides

Abstract Motivation The rational design of antimicrobial peptides (AMPs) with increased therapeutic potential requires deep understanding of the determinants of their activities. Inspired by the computational linguistic approach, we hypothesized that sequence patterns may encode the functional features of AMPs. Results We found that α-helical and β-sheet peptides have non-intersecting pattern sets and therefore constructed new sequence templates using only helical patterns. Designed peptides adopted an α-helical conformation upon binding to lipids, confirming that the method captures structural and biophysical properties. In the antimicrobial assay, 5 of 7 designed peptides exhibited activity against Gram(+) and Gram(–) bacteria, with most potent candidate comparable to best natural peptides. We thus conclude that sequence patterns comprise the structural and functional features of α-helical AMPs and guide their efficient design. Supplementary information Supplementary data are available at Bioinformatics online.

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Antimicrobial Activities and Structures of Two Linear Cationic Peptide Families with Various Amphipathic β-Sheet and α-Helical Potentials

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.12.4957-4964.2005 ◽

2005 ◽

Vol 49 (12) ◽

pp. 4957-4964 ◽

Cited By ~ 70

Author(s):

Yi Jin ◽

Janet Hammer ◽

Michelle Pate ◽

Yu Zhang ◽

Fang Zhu ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Peptides ◽

Plasma Membranes ◽

Membrane Lipids ◽

Lipid Vesicles ◽

Selective Advantage ◽

Antimicrobial Activities ◽

Helical Conformation ◽

Bacterial Cells ◽

Β Sheet

ABSTRACT Many naturally occurring antimicrobial peptides comprise cationic linear sequences with the potential to adopt an amphipathic α-helical conformation. We designed a linear 18-residue peptide that adopted an amphipathic β-sheet structure when it was bound to lipids. In comparison to a 21-residue amphipathic α-helical peptide of equal charge and hydrophobicity, this peptide possessed more similar antimicrobial activity and greater selectivity in binding to and inducing leakage in vesicles composed of bacterial membrane lipids than vesicles composed of mammalian membrane lipids (J. Blazyk, R. Weigand, J. Klein, J. Hammer, R. M. Epand, R. F. Epand, W. L. Maloy, and U. P. Kari, J. Biol. Chem. 276:27899-27906, 2001). Here, we compare two systematically designed families of linear cationic peptides to evaluate the importance of amphipathicity for determination of antimicrobial activity. Each peptide contains six lysine residues and is amidated at the carboxyl terminus. The first family consists of five peptides with various capacities to form amphipathic β-sheet structures. The second family consists of six peptides with various potentials to form amphipathic α helices. Only those peptides that can form a highly amphipathic structure (either a β sheet or an α helix) possessed significant antimicrobial activities. Striking differences in the abilities to bind to and induce leakage in membranes and lipid vesicles were observed for the two families. Overall, the amphipathic β-sheet peptides are less lytic than their amphipathic α-helical counterparts, particularly toward membranes containing phosphatidylcholine, a lipid commonly found in mammalian plasma membranes. Thus, it appears that antimicrobial peptides that can form an amphipathic β-sheet conformation may offer a selective advantage in targeting bacterial cells.

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New Antibacterial Peptides from the Freshwater Mollusk Pomacea poeyana (Pilsbry, 1927)

Biomolecules ◽

10.3390/biom10111473 ◽

2020 ◽

Vol 10 (11) ◽

pp. 1473

Author(s):

Melaine González García ◽

Armando Rodríguez ◽

Annia Alba ◽

Antonio A. Vázquez ◽

Fidel E. Morales Vicente ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Galleria Mellonella ◽

Random Coil ◽

Helical Conformation ◽

Moderate Activity ◽

Human Pathogens ◽

Spectra Analysis ◽

Bacterial Membranes ◽

Innate Defense

Antimicrobial peptides (AMPs) are biomolecules with antimicrobial activity against a broad group of pathogens. In the past few decades, AMPs have represented an important alternative for the treatment of infectious diseases. Their isolation from natural sources has been widely investigated. In this sense, mollusks are promising organisms for the identification of AMPs given that their immune system mainly relies on innate response. In this report, we characterized the peptide fraction of the Cuban freshwater snail Pomacea poeyana (Pilsbry, 1927) and identified 37 different peptides by nanoLC-ESI-MS-MS technology. From these peptide sequences, using bioinformatic prediction tools, we discovered two potential antimicrobial peptides named Pom-1 (KCAGSIAWAIGSGLFGGAKLIKIKKYIAELGGLQ) and Pom-2 (KEIERAGQRIRDAIISAAPAVETLAQAQKIIKGG). Database search revealed that Pom-1 is a fragment of Closticin 574 previously isolated from the bacteria Clostridium tyrobutyrium, and Pom-2 is a fragment of cecropin D-like peptide first isolated from Galleria mellonella hemolymph. These sequences were chemically synthesized and evaluated against different human pathogens. Interestingly, structural predictions of both peptides in the presence of micelles showed models that comprise two alpha helices joined by a short loop. The CD spectra analysis of Pom-1 and Pom-2 in water showed for both structures a high random coil content, a certain content of α-helix and a low β-sheet content. Like other described AMPs displaying a disordered structure in water, the peptides may adopt a helical conformation in presence of bacterial membranes. In antimicrobial assays, Pom-1 demonstrated high activity against the Gram-negative bacteria Pseudomonas aeruginosa and moderate activity against Klebsiella pneumoniae and Listeria monocytogenes. Neither of the two peptides showed antifungal action. Pom-1 moderately inhibits Zika Virus infection but slightly enhances HIV-1 infectivion in vitro. The evaluation of cell toxicity on primary human macrophages did not show toxicity on THP-1 cells, although slight overall toxicity was observed in high concentrations of Pom-1. We assume that both peptides may play a key role in innate defense of P. poeyana and represent promising antimicrobial candidates for humans.

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Stimuli-responsive conformational transformation of antimicrobial peptides stapled with an azobenzene unit

New Journal of Chemistry ◽

10.1039/d0nj03409f ◽

2020 ◽

Vol 44 (35) ◽

pp. 14777-14780

Author(s):

Jeonghun Lee ◽

Hanwool Lee ◽

Chulhee Kim

Keyword(s):

Antimicrobial Peptides ◽

Uv Irradiation ◽

Reductive Cleavage ◽

Helical Conformation ◽

Conformational Transformation ◽

Stimuli Responsive

The effect of the azobenzene-stapling position on the triggered transformation of the helical conformation of KLA peptides in response to UV irradiation and reductive cleavage is investigated.

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