Nucleoside phosphonic acids III. A nucleoside phosphonic acid analog of UDP-glucose

• Published in: Biochimica et biophysica acta. General subjects Vol. 201; no. 3; pp. 416 - 424
• Main Authors: Bax, P.C., Morris, F., Rammler, D.H.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 24.03.1970
• Subjects: UDP-Glc-phosphonic acid; UDP-GlcUA-phosphonic acid; UDP-Glc; Glc-1- P; UDP-Gal; UDP-GlcUA; UDP-Gal-phosphonic acid
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/0304-4165(70)90160-1

This report describes the synthesis of analogs of UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal), and UDP-glucoronic acid which contain 5′-deoxyuridine 5′-phosphonic acid place of the nucleotide uridine 5′-phosphate. These substances have been tested as substrates for UDP-Glc dehydrogenase (EC 1.1.1.22), uridyl transferase (EC 2.7.7.9), and UDP-Gal-4-epimerase (EC 5.1.3.2). The glucose-containing analogs will serve as substrates for the first two enzymes but they do so inefficiently. The epimerization reaction with the galactose-containing analog cannot be catalyzed by the epimerase from bovine mammary glands. The synthesis of the coenzyme analogs uses a common activated intermediate, 5′-deoxyuridine 5′-phosphonopmorpholidate. The coenzymes are prepared by reacting this activated substance with the trialkylammonium salts of glucose 1-phosphate, galactose 1-phosphate and glucorinic acid 1-phosphate. The isolated yields of the coenzymes were about 60%. The purity of the coenzyme analogs was determined by chromatographic and electrophoretic methods and the structures were confirmed in the following manner: spectrophotometric analyses indicated that no substitution had occured on the uracil nucleus, mild hydrolysis provided only 5′-deoxyuridine 5′-phosphonic acid and carbohydrate derivative in the expected ratio of 1:1 and the phosphorus to uracil ratio of 2:1. The trialkylammonium salts of coenzyme analogs failed to crystallize. A discussion of the chemistry of these analogs and the reasons for the enzyme systems used to test them is given.