ChemInform Abstract: Temperature‐Dependent Low‐Resolution Microwave Studies of m‐ Iodoanisole, m‐Bromoanisole, m‐Nitroanisole and m‐Anisaldehyde.

Sorenson, Sterling A.; True, Nancy S.; Ott, Christopher M.; Bohn, Robert K.; Farag, M. S.

doi:10.1002/chin.199233042

Cited by 1 publication

(2 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, Wakabayashi et al (4,11) and Strom et al (12) have shown that N-acylation of derivatives based on a sequence of bovine lactoferricin B (amino acids 17-41) resulted in higher * This work was supported in part by EC-specific RTD Programme Grant QLK2-CT-2002-01001, "Antimicrobial Endotoxin Neutralizing Peptides to Combat Infectious Diseases." 1 Supported by German Science Foundation Grant AN301/5-1. 2 Present address: Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Rd., La Jolla, CA 92037.…”

Section: Lactoferrin (Lf)mentioning

confidence: 99%

“…5 is an iron-binding glycoprotein found in milk (1) and in exocrine secretions of mammals as well as in granules and neutrophils during inflammatory responses (2,3). The pepsin cleavage fragment lactoferricin, comprising amino acid residues 1-45 of the N terminus of human LF and 17-41 of bovine LF, is one example of naturally occurring antimicrobial peptides (4).…”

Section: Lactoferrin (Lf)mentioning

confidence: 99%

See 1 more Smart Citation

Studies on Lactoferricin-derived Escherichia coli Membrane-active Peptides Reveal Differences in the Mechanism of N-Acylated Versus Nonacylated Peptides

Zweytick

Deutsch

Andrä

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

To improve the low antimicrobial activity of LF11, an 11-mer peptide derived from human lactoferricin, mutant sequences were designed based on the defined structure of LF11 in the lipidic environment. Thus, deletion of noncharged polar residues and strengthening of the hydrophobic N-terminal part upon adding a bulky hydrophobic amino acid or N-acylation resulted in enhanced antimicrobial activity against Escherichia coli, which correlated with the peptides' degree of perturbation of bacterial membrane mimics. Nonacylated and N-acylated peptides exhibited different effects at a molecular level. Nonacylated peptides induced segregation of peptide-enriched and peptide-poor lipid domains in negatively charged bilayers, although N-acylated peptides formed small heterogeneous domains resulting in a higher degree of packing defects. Additionally, only N-acylated peptides perturbed the lateral packing of neutral lipids and exhibited increased permeability of E. coli lipid vesicles. The latter did not correlate with the extent of improvement of the antimicrobial activity, which could be explained by the fact that elevated binding of N-acylated peptides to lipopolysaccharides of the outer membrane of Gram-negative bacteria seems to counteract the elevated membrane permeabilization, reflected in the respective minimal inhibitory concentration for E. coli. The antimicrobial activity of the peptides correlated with an increase of membrane curvature stress and hence bilayer instability. Transmission electron microscopy revealed that only the N-acylated peptides induced tubular protrusions from the outer membrane, whereas all peptides caused detachment of the outer and inner membrane of E. coli bacteria. Viability tests demonstrated that these bacteria were dead before onset of visible cell lysis. Lactoferrin (LF)5 is an iron-binding glycoprotein found in milk (1) and in exocrine secretions of mammals as well as in granules and neutrophils during inflammatory responses (2, 3). The pepsin cleavage fragment lactoferricin, comprising amino acid residues 1-45 of the N terminus of human LF and 17-41 of bovine LF, is one example of naturally occurring antimicrobial peptides (4). Lactoferricin displays activity against a diverse range of microorganisms such as Gram-negative bacteria, Gram-positive bacteria, yeast, and filamentous fungi, including a number of antibiotic-resistant pathogens (4). It is assumed that lactoferricin permeabilizes cell membranes and exerts anti-endotoxic activity by binding to lipopolysaccharides (4). In earlier studies, we demonstrated that the stretch of 11 amino acid residues (LF11, FQWQRNIRKVR-NH 2 ) corresponding to LF residues 21-31 exhibits only weak antibacterial activity against a number of Gram-positive and Gram-negative bacterial strains (5, 6). A series of about 150 LF11 mutants was designed with the aim to strengthen membrane-peptide interactions and hence to generate highly antimicrobial and endotoxin-neutralizing peptides, while having no or little antigenic or toxic effect on humans. Our stra...

show abstract