| Autor: |
Tuin, A.W. |
| Přispěvatelé: |
Overkleeft, H.S., Noort, D., Overhand, M., Leiden University |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| Předmět: |
|
| Zdroj: |
None |
| Popis: |
The last decade has witnessed an increased occurrence of bacterial resistance against antibiotics. The first part of this thesis describes the discovery of a novel target, protein kinase B / Akt1, that may be used to combat infection with pathogenic bacteria like Salmonella typhimurium. Inhibitors of this enzyme are currently being developed as anti-tumor agents. These molecules can now also be seen as potential antibiotics. The synthesis and biological evaluation of several series of new inhibitors of this enzyme are described. This resulted in the identification of a compound with sufficient potency and selectivity to allow in vivo inhibition of Salmonella outgrowth. The second part describes the optimization of an existing antibiotic, Gramicidin S. This is a naturally occurring decapeptide that disrupts the cellular membrane of bacteria. This results in leakage of intracellular contents and bacterial death. Unfortunately, Gramicidin S is toxic for red blood cells since their membrane is also destroyed. As part of an ongoing project to reduce the toxicity against red blood cells, part of the original decapeptide is replaced by synthetic molecules. One compound showed similar activity against bacteria and reduced toxicity against red blood cells. Further research is needed to further improve this antibiotic. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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