Fission impossible: Non-hydrolyzable nucleotide analogs
Crucial cellular processes such as transport, motion and division are orchestrated by a highly diverse set of regulatory phosphatases. Non-hydrolyzable analogs of nucleotides trap these enzymes in their various biologically relevant states and are thus essential tools for biochemical studies.
What does „non-hydrolyzable“ mean?
Non-hydrolyzable nucleotides have been chemically tweaked so enzymes can not cleave their phosphate chain the way they normally would. This is achieved by replacing one of the oxygen atoms in the phosphate chain with something the enzymes can not cut or only cut with significantly lower efficiency - commonly an imido group (–NH–), a methylene group (–CH2–), or a sulfur atom (–S) (Fig. 1).
More than twenty years of expertise in synthesizing non-hydrolyzable analogs led to a comprehensive non-hydrolyzable nucleotide portfolio (Figure 1) e.g. ideally suited for
- identification of protein-protein interactions and enzyme substrates
- elucidation of structure and dynamics of protein-nucleotide-complexes
- kinetic analysis of nucleotide exchange reactions on NTPase
Figure 1: Phosphate chain modifications leading to non-hydrolyzable nucleotides.
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