Abstract：
:The design and synthesis of 5-fluoro-6-[(2-aminoimidazol-1-yl)methyl]uracil (AIFU), a potent inhibitor of thymidine phosphorylase (TP) with K(i)-values of 11nM (ecTP) and 17nM (hTP), are described. Kinetic studies established that the type of inhibition of TP by AIFU is uncompetitive with respect to inorganic phosphate (or arsenate). The results obtained suggest that AIFU and other zwitterionic thymine analog inhibitors of TP act as transition state analogs, mimicking the anionic thymine leaving group, consistent with an S(N)2-type catalytic mechanism, and anchored by their protonated side chains to the enzyme-bound phosphate by electrostatic and H-bonding interactions.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Jain HV,Rasheed R,Kalman TIdoi
10.1016/j.bmcl.2010.01.076subject
Has Abstractpub_date
2010-03-01 00:00:00pages
1648-51issue
5eissn
0960-894Xissn
1464-3405pii
S0960-894X(10)00088-0journal_volume
20pub_type
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