Projects / Programmes source: ARRS

Structural-based neutralization of endotoxin by peptides

Research activity

Code Science Field Subfield
1.09.00  Natural sciences and mathematics  Pharmacy   

Code Science Field
B470  Biomedical sciences  Physiology 
LPS; immune response, peptidic inhibitors of LPS; molecular recognition; rational drug design
Evaluation (rules)
source: COBISS
Researchers (8)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  18675  Robert Bremšak    Technician  2004 - 2007  11 
2.  17915  PhD Helena Gradišar  Biotechnical sciences  Researcher  2004 - 2006  125 
3.  23940  PhD Boštjan Japelj  Natural sciences and mathematics  Junior researcher  2004 - 2007  37 
4.  06628  PhD Roman Jerala  Natural sciences and mathematics  Researcher  2004 - 2007  1,141 
5.  17917  PhD Andreja Majerle  Biotechnical sciences  Researcher  2004 - 2007  92 
6.  12048  PhD Marjetka Podobnik  Natural sciences and mathematics  Researcher  2007  291 
7.  12060  PhD Primož Pristovšek  Natural sciences and mathematics  Principal Researcher  2004 - 2007  135 
8.  22575  PhD Primož Šket  Natural sciences and mathematics  Researcher  2007  211 
Organisations (1)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0104  National Institute of Chemistry  Ljubljana  5051592000  21,093 
Lipopolysaccharide (LPS) triggers a series of defense reaction in the body that may lead to septic shock which is a leading cause of death in intensive care units and according to estimates, causes in the European union more than 150.000 casualties annually. One of the important strategies of preventing sepsis is aimed at its neutralization by specific binding of peptides that are derived from natural defense proteins or peptides. In continuation of our previous work where we have determined the bound tertiary structures of a series of peptides we will study additional structural aspects of LPS binding to peptidic inhibitors. We will determine the peptide stuctures when bound to LPS using NMR techniques while we approach the structures of the complex using computer modeling. We plan to refine the pharmacophore - the common LPS binding motif that we have already extended in our previous work by evaluating besides electrostatic also hydrophobic interactions. The course of action will include repeated cycles of designing new peptides with altered properties, their synthesis, structure analysis and determination of their characteristics, e.g. binding of LPS (Kd), neutralization of cell activation by LPS and any toxicity towards human cells. All the necessary equipment and knowledge for the execution of such a complex task is available in the research group. We expect that the project will provide the basis for rational design of novel peptide inhibitors of LPS activity.
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