Structure-based design of a bisphosphonate 5′(3′)-deoxyribonucleotidase inhibitor
作者： Petr Pachl , Ondřej Šimák , Pavlína Řezáčová , Milan Fábry , Miloš Buděšínský
DOI: 10.1039/C5MD00235D
关键词: Bisphosphonate 、 Phosphate ion 、 Nucleoside 、 Stereochemistry 、 Phosphomonoesters 、 Enzyme 、 Nucleotide 、 Biochemistry 、 Nucleoside analogue 、 Structure based 、 Chemistry
摘要: Cellular 5′-nucleotidases regulating nucleotide/nucleoside pools are capable of dephosphorylating phosphomonoesters important nucleoside analogue drugs, thus decreasing their therapeutic efficacy. Based on previously known inhibitor–enzyme complex structures, we developed a promising inhibitor by mimicking the phosphate ion and achieved 50- 100-fold increases in inhibitory potency towards cdN mdN, respectively. Crystal structures both complexes showed major differences binding mode enzymes.
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