TY - JOUR
T1 - Effect of folate diastereoisomers on the binding of 5-fluoro-2'-deoxyuridine-5'- monophosphate to thymidylate synthase
AU - Van Der Wilt, Clasina L.
AU - Pinedo, Herbert M.
AU - Jong, Marion De
AU - Peters, Godefridus J.
PY - 1993/3/9
Y1 - 1993/3/9
N2 - A series of natural and unnatural stereoisomers of reduced folate coenzymes have been studied for their capacity to facilitate binding of 5-fluoro-2'-dUMP (FdUMP) to bacterial thymidylate synthase (TS). The natural cosubstrate for the enzyme, (6R)-5,10-methylene-tetrahydrofolate (CH2-H4-folate), was 4-fold more potent than the unnatural 6S-form in promoting FdUMP binding to TS, but in a racemic mixture the effect of the 6R-form was not affected by the 6S-form. FdUMP binding to TS was also stimulated by tetrahydrofolate and dihydrofolate (85% and 30% as compared to (6RS)-CH2-H4-folate, respectively), but not by the stereoisomers of 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate (leucovorin). These results suggest that folates, which are not a natural cosubstrate for TS, have an additional role in facilitating FdUMP binding to TS.
AB - A series of natural and unnatural stereoisomers of reduced folate coenzymes have been studied for their capacity to facilitate binding of 5-fluoro-2'-dUMP (FdUMP) to bacterial thymidylate synthase (TS). The natural cosubstrate for the enzyme, (6R)-5,10-methylene-tetrahydrofolate (CH2-H4-folate), was 4-fold more potent than the unnatural 6S-form in promoting FdUMP binding to TS, but in a racemic mixture the effect of the 6R-form was not affected by the 6S-form. FdUMP binding to TS was also stimulated by tetrahydrofolate and dihydrofolate (85% and 30% as compared to (6RS)-CH2-H4-folate, respectively), but not by the stereoisomers of 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate (leucovorin). These results suggest that folates, which are not a natural cosubstrate for TS, have an additional role in facilitating FdUMP binding to TS.
UR - http://www.scopus.com/inward/record.url?scp=0027395111&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027395111&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(93)90267-Z
DO - 10.1016/0006-2952(93)90267-Z
M3 - Article
C2 - 8461049
AN - SCOPUS:0027395111
SN - 0006-2952
VL - 45
SP - 1177
EP - 1179
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 5
ER -