BIOMAT Database Logo BIOMAT Database Logo

Targeting 5'-deoxy-5'-(methylthio)adenosine phosphorylase by 5'-haloalkyl analogues of 5'-deoxy-5'-(methylthio)adenosine. 1991

J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, New York 14263.

A series of 5'-haloalkyl-modified analogues of 5'-deoxy-5'-(methylthio)adenosine (MTA), a nucleoside byproduct of polyamine biosynthesis, has been synthesized: 5'-deoxy-5'-[(2-monofluoroethyl)thio]adenosine (10), 5'-deoxy-5'-[(2-chloroethyl)thio]adenosine (4), 5'-deoxy-5'-[(2-bromoethyl)thio] adenosine (5), and 5'-deoxy-5'-[(3-monofluoropropyl)thio]adenosine (13). On the basis of their abilities to serve as substrates of MTA phosphorylase prepared from mouse liver, several of these analogues were characterized for their growth inhibitory effects in MTA phosphorylase-containing (murine L5178Y and human MOLT-4) and MTA phosphorylase-deficient (murine L1210 and human CCRF-CEM) leukemia cell lines. The MTA phosphorylase-containing tumor cell lines, especially of human origin, were found to be more sensitive to treatment by these analogues. Of the analogue series, 10 was the most potent inhibitor of growth in each of the cell lines tested. The analogues, especially compound 10, displayed a reduced capacity to alter polyamine pools relative to MTA, mechanistically indicating a decreased potential for interactions at sites other than MTA phosphorylase. The results indicate that of the analogues tested, compound 10 displayed the best inhibitor/substrate interaction with MTA phosphorylase, which, in turn, correlated with more potent growth inhibition in tumor cell lines containing MTA phosphorylase. Overall, this supports the concept that MTA phosphorylase plays a role in the activation of such analogues.

UI MeSH Term Description Entries
D007939 Leukemia L1210 An experimental LYMPHOCYTIC LEUKEMIA of mice. Leukemia L 1210,L 1210, Leukemia,L1210, Leukemia
D007942 Leukemia, Experimental Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues. Experimental Leukemia,Experimental Leukemias,Leukemia Model, Animal,Leukemias, Experimental,Animal Leukemia Model,Animal Leukemia Models,Leukemia Models, Animal
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011073 Polyamines Amine compounds that consist of carbon chains or rings containing two or more primary amino groups. Polyamine
D011683 Purine-Nucleoside Phosphorylase An enzyme that catalyzes the reaction between a purine nucleoside and orthophosphate to form a free purine plus ribose-5-phosphate. EC 2.4.2.1. Inosine Phosphorylase,Nicotinamide Riboside Phosphorylase,Purine Nucleoside Phosphorylases,Nucleoside Phosphorylases, Purine,Phosphorylase, Inosine,Phosphorylase, Nicotinamide Riboside,Phosphorylase, Purine-Nucleoside,Phosphorylases, Purine Nucleoside,Purine Nucleoside Phosphorylase,Riboside Phosphorylase, Nicotinamide
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D003839 Deoxyadenosines Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule. Adenine Deoxyribonucleosides,Adenylyldeoxyribonucleosides,Deoxyadenosine Derivatives,Deoxyribonucleosides, Adenine,Derivatives, Deoxyadenosine
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
Analogs of 5'-deoxy-5'-(methylthio)adenosine.
November 1974, Journal of medicinal chemistry,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
Mutagenic and comutagenic action of 5'-deoxy-5'-(methylthio)adenosine.
June 1986, Mutation research,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
Myocardial 5'deoxy-5'methylthioadenosine phosphorylase.
January 1994, Advances in experimental medicine and biology,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
[Analogues of adenosine 5'-diphosphate as inhibitors of polynucleotide phosphorylase: 2'-deoxyadenosine 5'-diphosphate, adenosine 5'-methylene diphosphonate, and adenosine 5'-hypophosphate].
July 1972, Biochimica et biophysica acta,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
Direct and tumor microenvironment mediated influences of 5'-deoxy-5'-(methylthio)adenosine on tumor progression of malignant melanoma.
February 2009, Journal of cellular biochemistry,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
Antitrypanosomal activity of 5'-deoxy-5'-(iodomethylene)adenosine and related 6-N-cyclopropyladenosine analogues.
March 2006, Journal of medicinal chemistry,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
The role of 5'-deoxy-5'-methyl thioadenosine phosphorylase in cardiac adenosine breakdown and adenine production.
January 2000, Advances in experimental medicine and biology,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
Activation of 5'-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors.
January 1983, Chemical & pharmaceutical bulletin,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
Radical SAM activation of the B12-independent glycerol dehydratase results in formation of 5'-deoxy-5'-(methylthio)adenosine and not 5'-deoxyadenosine.
February 2011, Biochemistry,
J R Sufrin, and A J Spiess, and D L Kramer, and P R Libby, and J T Miller, and R J Bernacki, and Y H Lee, and R T Borchardt, and C W Porter
5'-Deoxy-5'-methylthioadenosine phosphorylase--III. Role of the enzyme in the metabolism and action of 5'-halogenated adenosine analogs.
February 1985, Biochemical pharmacology,
Copied contents to your clipboard!