1,721,006 research outputs found
Uno Studio sulle Caratteristiche strutturali e redox di complessi ternari del rame con proprietà auxiniche
No full textEPR and X-Ray Structure Characterization of Ternary Complexes of Copper(II) and Auxins with Phenanthrolines
No full textCoordination Modes of Histidine Moiety in Copper(II) Dipeptide Complexes Detected by Multifrequency ESR
No full textArginine-lysine swaps selectively enhance antimicrobial activity over cytotoxic activity of LL-37 peptide
No full textLL-37 is the only cationic peptide belonging to the cathelicidin family expressed in humans. LL-37 has bactericidal activity and exerts immunomodulatory functions, thus forming, together with other peptides, the first line of defense against infections. The formation of LL-37 aggregates in the presence of neutral membranes promotes lack of specificity for microbial cells, which could explain why LL-37 becomes cytotoxic towards eukaryotic cells at high concentrations. Cationic amino-acids such arginine (Arg) and lysine (Lys) are known determinants for bacterial killing; however very little is known about how Lys-Arg exchange can influence LL-37 biological activities. Since antimicrobial peptides are promising candidates for the development of novel anti-infective agents, we have compared the bactericidal and cytotoxic effects of five LL-37 variants with wild-type peptide. The bactericidal activity was tested against Escherichia coli and Streptococcus agalactiae, while cytotoxicity was measured against A549, a human bronchoepithelial cell line. We found clear differences in bacterial killing kinetics towards both pathogens when central Arg residues were mutated in Lys, with Arg more efficient than Lys in bacterial membrane permeation. Of interest, the Arg at position 34 can compensate for the absence of the Arg at position 19 and 23 and the presence of Lys at the other positions resulted in a diminished toxicity for eukaryotic cells. Our study sheds new light on key amino-acid residues of LL-37 and should be considered when novel cationic amphipathic peptides derived from LL-37 are designed
Structural and Functional Consequences Induced by Post-Translational Modifications in α-Defensins.
No full textHNP-1 is an antimicrobial peptide that undergoes proteolytic cleavage to become a mature peptide. This process represents the mechanism commonly used by the cells to obtain a fully active antimicrobial peptide. In addition, it has been recently described that HNP-1 is recognized as substrate by the arginine-specific ADP-ribosyltransferase-1. Arginine-specific mono-ADP-ribosylation is an enzyme-catalyzed post-translational modification in which NAD(+) serves as donor of the ADP-ribose moiety, which is transferred to the guanidino group of arginines in target proteins. While the arginine carries one positive charge, the ADP-ribose is negatively charged at the phosphate moieties at physiological pH. Therefore, the attachment of one or more ADP-ribose units results in a marked change of cationicity. ADP-ribosylation of HNP-1 drastically reduces its cytotoxic and antibacterial activities. While the chemotactic activity of HNP-1 remains unaltered, its ability to induce interleukin-8 production is enhanced. The arginine 14 of HNP-1 modified by the ADP-ribose is in some cases processed into ornithine, perhaps representing a different modality in the regulation of HNP-1 activitie
cis-trans Isomerization of β-casomorphin peptides bound to copper(II):: integration of EPR and NMR studies
No full textCopper complexes of beta -casomorphin peptides (BCM-7, BCM-5, BCM-4) were investigated by EPR and NMR in DMSO-d(6) solutions. Speciation of copper among many of the possible isomers was apparent. Computer simulations of low and room temperature EPR allowed the number of co-ordinated nitrogens in the major species (2 for BCM-4 and BCM-5, 4 for BCM-7) to be inferred and a rotational correlation time of 0.18 ns at 298 K to be evaluated for all complexes. All isomers of BCM-4 and BCM-5 were shown to bind copper, but the resulting structures were strictly determined by the conformational state of (2)Pro. The trans, rather than the cis, conformation was shown to allow binding of the deprotonated (3)Phe-NH; the terminal amino and carboxylate groups provided the other binding groups in all cases. Structures were obtained by constrained molecular dynamics using copper-proton distances obtained from paramagnetic nuclear relaxation rates. In the case of BCM-7, only the cis-cis-trans and/or the cis-cis-cis isomers were not binding copper. The conformational state of each Pro was shown to drive formation of the copper-nitrogen bond within the immediately adjacent residue, leading to the complex having four co-ordinated nitrogens in the case of the trans-trans-trans isomer
Evidence of Polyphenols Nitrosation by Computer aided ESR Spectroscopy
No full textPolyphenols play an important role as model systems in transition metal derivatives for the preparation of macromolecular systems. Among the metal ions ironnitrosyl coordination chemistry has received much attention in the past because of its important role in inorganic and biological processes. In the case of Fe(I)(NO)2 complexes with polyphenols ligands in solution, difficulties in the interpretation of the ESR spectra arise from complicated patterns due to simultaneous presence of different nitrogen nuclei directly bound to the metal ion or due to the presence of equilibria between species under slow exchange conditions. In order to overcome these difficulties the investigations reported here were carried out using computer simulation of ESR spectra combined with selective isotopic substitution of 14NO with 15NO. Resorcinol displays an unexpected nine lines ESR pattern at g=2.018 which can be explained only by considering more than two nitrogen atoms interacting with the unpaired electron delocalized over the metal complex. Copyright © 1992 Hüthig & Wepf Verla
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