Inhibition of Yersinia protein tyrosine phosphatase by phosphonate derivatives of calixarenes.
Inhibition of Yersinia protein tyrosine phosphatase by calix[4]arene mono-, bis-, and tetrakis(methylenebisphosphonic) acids as well as calix[4]arene and thiacalix[4]arene tetrakis(methylphosphonic) acids have been investigated. The kinetic studies revealed that some compounds in this class are potent competitive inhibitors of Yersinia PTP with inhibition constants in the low micromolar range. The binding modes of macrocyclic phosphonate derivatives in the enzyme active center have been explained using computational docking approach. The results obtained indicate that calix[4]arenes are promising scaffolds for the development of inhibitors of Yersinia PTP.
Vovk
Andriy I
AI
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska, 1, 02660 Kyiv-94, Ukraine. vovk@bpci.kiev.ua
Kononets
Lyudmyla A
LA
Tanchuk
Vsevolod Yu
VY
Cherenok
Sergiy O
SO
Drapailo
Andriy B
AB
Kalchenko
Vitaly I
VI
Kukhar
Valery P
VP
D001665:Binding Sites; D047250:Calixarenes / Q000737:chemistry* / Q000494:pharmacology; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D063065:Organophosphonates / Q000737:chemistry; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015007:Yersinia / Q000187:drug effects
D004791:Enzyme Inhibitors; D063065:Organophosphonates; D047250:Calixarenes; D017027:Protein Tyrosine Phosphatases