Projects / Programmes
Development of gyrase inhibitors and peptides as antimicrobial agents
| Code |
Science |
Field |
Subfield |
| 4.06.00 |
Biotechnical sciences |
Biotechnology |
|
| Code |
Science |
Field |
| T490 |
Technological sciences |
Biotechnology |
| B230 |
Biomedical sciences |
Microbiology, bacteriology, virology, mycology |
| B510 |
Biomedical sciences |
Infections |
antimicrobial drugs, molecular modeling, DNA gyrase, peptides, permeabilization, NMR spectroscopy, fluorescence, microbial biotechnology
Researchers (7)
Organisations (1)
| no. |
Code |
Research organisation |
City |
Registration number |
No. of publicationsNo. of publications |
| 1. |
0104 |
National Institute of Chemistry |
Ljubljana |
5051592000 |
20,996 |
Abstract
Due to the development of resistance to generally used antibiotics bacterial infections are again becoming an important medical problem. Therefore development of novel antimicrobial compounds or/and improvement of their application is required. Modern rational drug design of pharmacologically active compounds is based on the knowledge of tertiary structures of targets and their interactions with drugs. We intend to combine and extend the research of two types of antimicrobial compounds, which in combination exhibit synergistic activity. In the previous project we have identified a natural flavonoid quercetin as a potent inhibitor of bacterial gyrase and established its mode of action. In continuation we will test inhibitory activity against gyrases of a series of naturally produced and commercially available compounds belonging to the flavonoid and catechin type, which are often present in traditional human diet such as in green tea. We will use SAR analysis to identify the functional groups that influence the activity. As the second group of antimicrobial compounds we will design and test activity of short, 6-18 residue cationic antimicrobial peptides, originating from the sequences of human defense peptides and proteins. Based on the tertiary structure information of selected peptides in complex with lipids, which will be determined by NMR and biological activities we will enhance the permeabilization of bacterial cells by peptides. We will also measure the penetration of peptides into bacterial cells and their binding to other intracellular targets such as DNA. Combinations of gyrase inhibitors and peptides with the strongest synergistic effect will be identified. Selected peptides will be prepared in recombinant form as the more economical biotechnological alternative of production.
