Sarah Clark’s report

1st European Chemistry Congress – Budapest—August 2006

The 1st European Chemistry Congress in Budapest was a showcase for ongoing work in chemical science across Europe, with chemical and molecular scientists from industry, academia and government institutions in Europe and from around the world in attendance. The scientific programme included plenary, keynote and invited lectures as well as oral communications and poster sessions. Plenary lectures were given by Nobel Laureates and keynote lectures discussed important areas of chemistry, while invited lectures focussed on the latest developments in a wide variety of topics.

My work at Queen’s University Belfast focuses on the synthesis of 2-fluoromethyl nucleoside analogues as potential antiviral agents. I presented a poster on my research into the syntheses of 2’-C-fluoromethyl cytosine and 2’, 3’-dideoxy-2’-C-fluoromethyl-3’-hydroxymethyl nucleosides, and the interesting methodologies used. Nucleosides make up part of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), either one of which is present in the genetic material of viruses.

Viruses use host cells to reproduce new viral cells by taking over the cell’s normal functions and using them to replicate new viral genetic material causing the host cell to die. These new viral cells go on to infect other cells in a similar fashion. Analogues of nucleosides are exceedingly useful as they can be incorporated into the viral DNA during replication but, not being the natural nucleoside, they prevent the replication process from continuing hence preventing new viral particles from being produced. Nucleoside analogues are a vital class of compounds that have been at the forefront of antiviral chemotherapy for the past 30 years.

At present, at least 16 analogues are licensed for use as antiviral drugs, yet none of these analogues contain a fluorine atom in place of one or more hydrogen atoms in the sugar moiety. This is a very common strategy for improving the biological activity profiles of drugs as fluorine enhances the lipophilicity of a molecule and hence its distribution within an organism. Fluorine also provides greater stability, making a drug more resistant to metabolic degradation and transformation.

Placing a fluorine at C-2’ stabilises the glycosidic bond and therefore a series of 2’-C-fluorinated nucleoside analogues have been synthesised in the hope of producing more effective drugs with antiviral or anticancer properties. In the future, I am hoping to test the compounds I have made against common viruses such as herpes simplex virus (HSV), hepatitis A, B, C (HAV, HBV, HCV), cytomegalovirus (CMV) and influenza, for antiviral activity. Humanimmunodeficiency virus (HIV) is another virus that the compounds will be tested against. HIV/AIDS (acquired immune deficiency syndrome) has reached epidemic proportions with almost 40 million people infected globally. In Britain, roughly 73,000 cases of HIV had been reported as of June 2005, with nearly 22,000 of those people being diagnosed with AIDS. HIV uses T-helper lymphocytes as their host cells for viral replication.

T-helper lymphocytes are key components in the immune system and therefore lymphocyte cell death leads to an HIV-infected patient becoming more susceptible to common infections which eventually lead to death. The 1st European Chemistry Congress kept me up to date with the latest developments in my field of work and also helped me to improve my knowledge in other areas of chemistry and biology. I also had the opportunity to learn about careers in chemistry which was a great help to me in the final year of my PhD. The conference aided me in networking skills and improved my ability to communicate my research to fellow students and academics, and also to those who work in other areas of expertise.

Sarah Clark