Development of gyrase inhibitors and peptides as antimicrobial agents

Code

J4-6129 (D) - included in ARRS records

Head

PhD Roman Jerala

Period

2/1/2004 - 1/30/2007

Range in 2007

0.12 FTE

Science

Natural sciences and mathematics (3)
Biotechnical sciences (3)
Other (1)

Reseacher status

Researcher (6)
Junior expert or technical associate (1)
Junior researcher (0)
Researcher/expert (0)
Private researcher (0)

Education

Doctor's degree (6)
Other (1)

Sex

Woman (3)
Man (4)

Status

Active (7)

No. of publications

10–99 (3)
100–999 (3)
1,000–9,999 (1)

Projects / Programmes source: ARRS

source: ARRS

Development of gyrase inhibitors and peptides as antimicrobial agents

Research activity

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

Keywords

antimicrobial drugs, molecular modeling, DNA gyrase, peptides, permeabilization, NMR spectroscopy, fluorescence, microbial biotechnology

Evaluation (rules)

source: COBISS

Citations Citations for bibliographic records in COBIB.SI that are linked to records in citation databases

source: WoS

source: Scopus

source: COBISS

Researchers (7)

no.	Code	Name and surname	Research area	Role	Period	No. of publicationsNo. of publications
1.	14360	PhD Mojca Benčina	Biotechnical sciences	Researcher	2007	378
2.	18675	Robert Bremšak		Technician	2004 - 2007	11
3.	17915	PhD Helena Gradišar	Biotechnical sciences	Researcher	2004 - 2007	125
4.	23940	PhD Boštjan Japelj	Natural sciences and mathematics	Junior researcher	2004 - 2007	37
5.	06628	PhD Roman Jerala	Natural sciences and mathematics	Principal Researcher	2004 - 2007	1,141
6.	17917	PhD Andreja Majerle	Biotechnical sciences	Researcher	2004 - 2007	92
7.	12060	PhD Primož Pristovšek	Natural sciences and mathematics	Researcher	2004 - 2007	135

Organisations (1)

no.	Code	Research organisation	City	Registration number	No. of publicationsNo. of publications
1.	0104	National Institute of Chemistry	Ljubljana	5051592000	21,093

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.