Linked Life Data

17389605

Source:http://linkedlifedata.com/resource/pubmed/id/17389605

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2007-5-14
pubmed:abstractText
The peptide NK-2 is an effective antimicrobial agent with low hemolytic and cytotoxic activities and is thus a promising candidate for clinical applications. It comprises the alpha-helical, cationic core region of porcine NK-lysin a homolog of human granulysin and of amoebapores of pathogenic amoeba. Here we visualized the impact of NK-2 on Escherichia coli by electron microscopy and used NK-2 as a template for sequence variations to improve the peptide stability and activity and to gain insight into the structure/function relationships. We synthesized 18 new peptides and tested their activities on seven Gram-negative and one Gram-positive bacterial strains, human erythrocytes, and HeLa cells. Although all peptides appeared unordered in buffer, those active against bacteria adopted an alpha-helical conformation in membrane-mimetic environments like trifluoroethanol and negatively charged phosphatidylglycerol (PG) liposomes that mimick the cytoplasmic membrane of bacteria. This conformation was not observed in the presence of liposomes consisting of zwitterionic phosphatidylcholine (PC) typical for the human cell plasma membrane. The interaction was paralleled by intercalation of these peptides into PG liposomes as determined by FRET spectroscopy. A comparative analysis between biological activity and the calculated peptide parameters revealed that the decisive factor for a broad spectrum activity is not the peptide overall hydrophobicity or amphipathicity, but the possession of a minimal positive net charge plus a highly amphipathic anchor point of only seven amino acid residues (two helical turns).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14719-28
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17389605-Amino Acid Sequence, pubmed-meshheading:17389605-Anti-Infective Agents, pubmed-meshheading:17389605-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:17389605-Cell Membrane, pubmed-meshheading:17389605-Erythrocytes, pubmed-meshheading:17389605-Gram-Negative Bacteria, pubmed-meshheading:17389605-HeLa Cells, pubmed-meshheading:17389605-Humans, pubmed-meshheading:17389605-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:17389605-Ion Channels, pubmed-meshheading:17389605-Liposomes, pubmed-meshheading:17389605-Microbial Sensitivity Tests, pubmed-meshheading:17389605-Peptides, pubmed-meshheading:17389605-Phosphatidylcholines, pubmed-meshheading:17389605-Protein Structure, Secondary, pubmed-meshheading:17389605-Protozoan Proteins, pubmed-meshheading:17389605-Sequence Homology, Amino Acid, pubmed-meshheading:17389605-Structure-Activity Relationship
pubmed:year
2007
pubmed:articleTitle
Rationale for the design of shortened derivatives of the NK-lysin-derived antimicrobial peptide NK-2 with improved activity against Gram-negative pathogens.
pubmed:affiliation
Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Parkallee 10, D-23845 Borstel, Germany. jandrae@fz-borstel.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't