Borononucleotides as substrates/binders for human NMP kinases: enzymatic and spectroscopic evaluation.
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.
Groupe 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
Chahrazade
C
El Amri
Anthony R
AR
Martin
Jean-Jacques
JJ
Vasseur
Michael
M
Smietana
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry; D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009703:Nucleoside-Phosphate Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000187:drug effects; D013942:Thymine Nucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D001897:Boronic Acids; D005456:Fluorescent Dyes; D013942:Thymine Nucleotides; D000255:Adenosine Triphosphate; D009703:Nucleoside-Phosphate Kinase