RESEARCH TOPICS:

1.   Independent synthesis of putative products of oxidative DNA damage.

2.   Synthesis and structural studies of inhibitors of the glycogen phosphorylase enzyme, as potential antidiabetic drugs.

3.   Online Optical Probes for the Quality Control and Safety Assessment of Olive and Other Edible Oils. (PROBEOIL)

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1.   Independent synthesis of putative products of oxidative DNA damage.

 

Oxidative DNA damage is an important biological event, the complexity of which renders difficult to impossible the study of the mechanisms involved in most of the important degradation pathways. At the same time biologists need to determine the mutation potential of each stable lesion whether this is a base alteration, single or double strand break in an isolated DNA domain or as part of a clustered group of lesions located in either the inter-histone vulnerable DNA zone or transfered through phenomena such as DNA charge transport within the histone-protected DNA region.

We have approached these problems through the following lines of research efforts:

  •    Independent synthesis of putative products of oxidative DNA damage
  •    Independent generation of putative intermediates in DNA damage

Most of the existing studies in this area have focused on the isolation and characteri-zation of new products of oxidative DNA damage as well as the quantification of the biological role of the specific lesion in oxidative stress.

The independent synthesis of reported relatively stable oxidation products of natural nucleosides serves the purpose of validating the reported structures as these have been revealed mainly from spectroscopic investigations, carrying out stability studies in order to determine the biological impact of such a lesion and producing these lesions in sufficient amounts for insertion in synthetic oligonucleotides and carrying out biological studies in order to determine the mutation potential of each lesion.



 

 

 

 

2.   Synthesis and structural studies of inhibitors of the glycogen phosphorylase enzyme, as potential antidiabetic drugs.

 

 

The aim of this research project is synthesis, biochemical and structural characterization of new, potential hypoglycemic drugs as inhibitors of glycogen phosphorylase (GP). GP is one of the enzymes which are directly related to the breakdown of glycogen in the liver. Previous studies have shown that it is a good molecular target for the design and synthesis of new potential inhibitors of glycogenolysis, with the aim of maintaining normal glucose levels in blood circulation. In this project, the Structure-Based-Drug-Design Approach is employed, using as target the catalytic site of GP. Beta-D-glucopyranosyl compounds are synthesized, their binding affinity to the catalytic site of GP is measured through enzyme kinetics experiments while their exact binding mode with the target is elucidated via X-ray crystallography. The information that is accumulated through this process leads to the design and synthesis of even more potent inhibitors.

 

 

Figure1 copy

Schematic diagram of RMGPb dimeric molecule viewed down the molecular dyad. The positions are shown for the active sites which are used as molecular targets for developing hypoglycemic drugs. The catalycis site is located in the centre of the molecule and access to it is restricted by the conformation of the loop 280s (residues 282-287, yellow). The catalytic site binds glucose-1-phosphate (the substrate of the enzyme) and glucose (inhibitor). The inhibitor site (green) is located in the entrance of the the catalytic site and is characterized by intense aromatic character due to the Phe285 and Tyr613 residues. It favours binding of flavopiridol, caffeine etc which inhibit RMGPb by acting synergistically with glucose. The allosteric site (purple) is located in the two subunits interface, in the central cavity of the dimer. It binds compounds such as glucopyranosylurea and benzimidazol. The glycogen storage site is located in the surface of the enzyme, and finally the benzimidazol site, which requires additional research in order to be characterized as a “target” for drug design. (Oikonomakos 2001; Chrysina et al., 2005).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


3.   Online Optical Probes for the Quality Control and Safety Assessment of Olive and Other Edible Oils. (PROBEOIL)

 

 

The main concept of the project is to develop a system for the non-destructive analysis of quality, authenticity and contamination main parameters in edible oils and olive oil specifically. More precisely, the goal of this cooperation will be to develop efficient online probes that will be able to monitor the optical spectra fingerprint of olives and olive oil during the various stages of the production process and during storage. Through the analysis, by the software developed, and database construction, the designed probes should be able  to monitor origin, authenticity and quality  (fatty acid composition, acidity, moisture and pigments content) and contamination from organic pollutants such as dioxins and PAHs. The probes will be able to measure light absorbance in selected regions of the ultraviolet-visible-near infrared and mid infrared range directly in the vessels processing olive oil or olive paste.