title: Human neutrophil peptide 1 variants bearing arginine modified cationic side chains: effects on membrane partitioning.
abstract: α-Defensins (e.g. human neutrophil peptides, HNPs) have a broad spectrum bactericidal activity contributing to human innate immunity. The positive charge of amino acid side chains is responsible for the first interaction of cationic antimicrobial peptides with negatively charged bacterial membranes. α-Defensins contain a high content of Arg residues compared to Lys. In this paper, different peptide analogs including substitution of Arg-14 respectively with N(G)-N(G')-asymmetric dimethyl-l-arginine (ADMA), N(G)-N(G')-symmetric dimethyl-l-arginine (SDMA) and Lys (R14K and R15KR14KR15K) variants have been studied to test the role of Arg guanidino group and the localized cationic charge of Lys for interaction with lipid membranes. Our findings show that all the variants have a decreased disruptive activity against the bilayer. The methylated analogs show a reduction in membrane partitioning due to the lack of their ability to form hydrogen bonds. Comparison with the native HNP-1 peptide has been discussed.
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Bonucci
authors.affiliation: School of Biosciences and Biotechnologies, University of Camerino, 62032 Camerino, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Balducci
authors.affiliation: Novartis Vaccines & Diagnostics, via Fiorentina 1, 53100 Siena, Italy.
authors.forename: Manuele
authors.initials: M
authors.lastname: Martinelli
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, 53100 Siena, Italy. Electronic address: rebecca.pogni@unisi.it.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pogni
mesh_terms: D001120:Arginine / Q000737:chemistry*; D002412:Cations / Q000737:chemistry; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D008958:Models, Molecular; D023084:alpha-Defensins / Q000737:chemistry*
chemical_list: D002412:Cations; D008051:Lipid Bilayers; D008563:Membrane Lipids; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D001120:Arginine; D008239:Lysine
keywords: Arginine modified side chains; Bacterial model membrane; HNP-1 variants; Reduced lipid–protein interaction; Spectroscopic techniques