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Based on the state-of-the-art DNA sequencing method - Sanger sequencing - the major aim of future research is to develop a cost-effective and gel electrophoresis-free sequencing method. These new sequencing technologies - such as the so-called sequencing-by-synthesis method (SBS) - should be able to detect DNA mutations faster and more accurate than the currently available sequencing technique. The function of a reversible terminator used for SBS is as follows: 3 -modified, dye-labeled nucleotides are incorporated by the polymerase complementary to the DNA-template (as already known from Sanger sequencing) stopping the DNA-synthesis immediately. After detection of the fluorescent signal, the reversible terminator has to be cleavable in such a way (here: the 3 -modification) that the DNA-synthesis can continue (i. e. reversible termination). Thus SBS enables a step-by-step chain elongation with a direct read-out of the sequence via fluorescent signals. This PhD thesis covers the synthesis of 3 -modified nucleosides as key compounds for these terminators and the evaluation of suitable 3 -modification cleavage conditions.

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Angelika C. Keller was born in Erlangen/Germany in 1979 and studied chemistry from 2000 to 2006 in Frankfurt/Main. She received her diploma in 2006 with the topic Synthesis of reversible terminators for SBS and continued the research on this subject during her PhD thesis which she finished in 2009.

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