Borononucleotides as substrates/binders for human NMP kinases: enzymatic and spectroscopic evaluation
Chahrazade El Amri1, Anthony R Martin, Jean-Jacques Vasseur
1Groupe d'Enzymologie Moléculaire et Fonctionnelle, UR4-UPMC, Université Pierre et Marie Curie, Sorbonne Universités, case courrier 256, 7, quai St Bernard, 75252 Paris Cedex 05, France. chahrazade.el_amri@upmc.fr
Abstract:
Borononucleotides are a family of natural nucleotide monophosphate analogues with a 5'-boronic acid function. As B-O-P linkages are known to be unstable in solution, we evaluated the ability of borononucleotides to be recognized by nucleoside monophosphate kinases and eventually foil the phosphorylation process. In this context, and with the idea of probing the influence of their size, shape, and flexibility, a library of borononucleotides were synthetized starting from the borononucleotide analogue of thymidine, which was shown to behave as a slow substrate of human TMP kinase. This study thus constitutes a good starting point for the development of new monophosphate mimics as potential substrates or ligands for NMP kinases.
