SYNTHESIS OF (6S)-5-FORMYLTETRAHYDROPTEROYLPOLYGLUTAMATES AND INTERCONVERSION TO OTHER REDUCED PTEROYLPOLYGLUTAMATE DERIVATIVES

被引:37
作者
STOVER, P [1 ]
SCHIRCH, V [1 ]
机构
[1] VIRGINIA COMMONWEALTH UNIV,DEPT BIOCHEM,RICHMOND,VA 23298
关键词
D O I
10.1016/0003-2697(92)90210-X
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
5-Formyltetrahydropteroylpolyglutamates can be synthesized and purified directly from dihydropteroylpolyglutamates in a single-step procedure without purification of intermediates and with yields greater than 90%. The procedure involves a coupled enzymatic synthesis of 10-formyltetrahydropteroylpolyglutamates using the enzymes dihydrofolate reductase, serine hydroxymethyltransferase, and C1-tetrahydrofolate synthase with catalytic amounts of NADPH. The 10-formyltetrahydropteroylpolyglutamates are subsequently converted to 5-formyltetrahydropteroylpolyglutamates at 90°C with near quantitative yields. 5-Formyltetrahydropteroylpolyglutamates are the only stable reduced derivatives of tetrahydropteroylpolyglutamates and can be purified and stored indefinitely without decomposition. Additionally, 5-formyltetrahydropteroylpolyglutamates can be readily converted to other derivatives of tetrahydropteroylpolyglutamates with yields greater than 95%. Also described is the synthesis of tetrahydropteroylglutamates labeled at C-11 with either 14C or 13C. Rapid purification procedures for serine hydroxymethyltransferase and C1-tetrahydrofolate synthase from frozen rabbit livers are presented. © 1992.
引用
收藏
页码:82 / 88
页数:7
相关论文
共 21 条
[1]   INHIBITION OF MAMMALIAN THYMIDYLATE SYNTHASE BY 10-FORMYLTETRAHYDROPTEROYLPOLYGLUTAMATE [J].
BALINSKA, M ;
RHEE, M ;
WHITELEY, JM ;
PRIEST, DG ;
GALIVAN, J .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1991, 284 (01) :219-222
[2]  
Cashmore A R, 1980, Methods Enzymol, V66, P459
[3]   A SIMPLE METHOD FOR PREPARATION OF 5-METHYLTETRAHYDROPTEROYLGLUTAMIC ACID [J].
CHANARIN, I ;
PERRY, J .
BIOCHEMICAL JOURNAL, 1967, 105 (02) :633-&
[4]   CHEMISTRY OF LEUCOVORIN [J].
COSULICH, DB ;
ROTH, B ;
SMITH, JM ;
HULTQUIST, ME ;
PARKER, RP .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1952, 74 (13) :3252-3263
[5]   CHANGES IN THE CHAIN-LENGTH OF FOLYLPOLYGLUTAMATES DURING LIVER-REGENERATION [J].
ETO, I ;
KRUMDIECK, CL .
LIFE SCIENCES, 1982, 30 (02) :183-189
[6]  
HOPKINS S, 1984, J BIOL CHEM, V259, P5618
[7]  
KISLIUK RL, 1991, CHEMTRACTS BIOCH MOL, V2, P217
[8]   STUDIES ON THE METHYLENE METHYL INTERCONVERSION CATALYZED BY METHYLENETETRAHYDROFOLATE REDUCTASE FROM PIG-LIVER [J].
MATTHEWS, RG .
BIOCHEMISTRY, 1982, 21 (17) :4165-4171
[9]   ENZYMATIC-SYNTHESIS AND FUNCTION OF FOLYLPOLYGLUTAMATES [J].
MCGUIRE, JJ ;
BERTINO, JR .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 1981, 38 (AUG) :19-48
[10]  
MCGUIRE JJ, 1984, FOLATES PTERINS, V1, P135