Abstract
The complex formed by isopentane, as a model for the isoleucine residue present in the wild-type thymidylate synthase, with 4-mercaptopyridine as a fragment of the thymidylate synthase inhibitor Thymitaq (AG337) is investigated with ab initio quantum chemical calculations at Hartree-Fock and MP2 levels, using the 3-21G* basis set. The binding energy is compared with the binding energies of 4-mercaptopyridine with amino acid residues found in mutant thymidylate synthase enzymes. As compared with isoleucine, alanine and glycine do not show binding, in agreement with enzyme-inhibition results.
MeSH terms
-
Acetamides / chemistry
-
Acetamides / metabolism
-
Amino Acids / chemistry
-
Amino Acids / metabolism*
-
Benzene / chemistry
-
Benzene / metabolism
-
Binding Sites
-
Electrons
-
Hydrogen / chemistry
-
Hydrogen / metabolism
-
Ions
-
Methane / chemistry
-
Methane / metabolism
-
Models, Chemical*
-
Pentanes / chemistry
-
Pentanes / metabolism
-
Pyridines / chemistry
-
Pyridines / metabolism*
-
Quinazolines / chemistry*
-
Quinazolines / metabolism
-
Quinazolines / pharmacology
-
Thermodynamics
-
Thymidylate Synthase / antagonists & inhibitors*
-
Thymidylate Synthase / chemistry
-
Thymidylate Synthase / genetics
-
Thymidylate Synthase / metabolism
Substances
-
Acetamides
-
Amino Acids
-
Ions
-
Pentanes
-
Pyridines
-
Quinazolines
-
4-thiopyridine
-
Hydrogen
-
acetamide
-
Thymidylate Synthase
-
Benzene
-
nolatrexed
-
Methane
-
isopentane