Phosphonoacetate was an effective inhibitor of both the Marek's disease herpesvirus- and the herpesvirus of turkey-induced DNA polymerase. Using the herpesvirus of turkey-induced DNA polymerase, phosphonoacetate inhibition studies for the DNA polymerization reaction and for the deoxyribonucleoside triphosphate-pyrophosphate exchange reaction were carried out. The results demonstrated that phosphonoacetate inhibited the polymerase by interacting with it at the pyrophosphate binding site to create an alternate reaction pathway. A detailed mechanism and rate equation for the inhibition were developed. For comparison to phosphonoacetate, pyrophosphate inhibition patterns and apparent inhibition constants were determined. Twelve analogues of phosphonoacetate were tested as inhibitors of the herpesvirus of turkey-induced DNA polymerase. At the concentrations tested, only one, 2-phosphonopropionate, was an inhibitor. The apparent inhibition constant for it was about 50 times greater than the corresponding apparent inhibition constant for phosphonoacetate. DNA polymerase alpha of duck embryo fibroblasts, the host cell for the herpesviruses, was inhibited by phosphonoacetate. The apparent inhibition constants for the alpha polymerase were about 10-20 times greater than the corresponding inhibition constants for the herpesvirus-induced DNA polymerase. Duck DNA polymerase beta, Escherichia coli DNA polymerase I, and avian myeloblastosis virus reverse transcriptase were not inhibited by phosphonoacetate.
The equilibrium composition ofcis andtrans isomers obtained by isomerizing oleic, linoleic, and linolenic acids with selenium or nitrous acid has been studied using gas chromatography and infrared spectroscopy. The oleic/elaidic equilibrium mixture was found to contain 75舑80% elaidic acid instead of the generally accepted 66% value. It is felt that the greater accuracy of gas chromatography and infrared analyses over older methods allows this equilibrium to be defined with greater precision.Similar studies on thecis‐trans isomerization of linoleic and linolenic acids indicated that their equilibrium mixtures also contained 75舑80%trans double bonds. With linoleic acid, thesetrans bonds were shown to be randomly distributed among the double bonds present.Cis‐trans isomerization of linoleic or linolenic acids with selenium produced by‐products having elution times equivalent to 18蝘2, 18蝘1, and 18蝘0 on a gas chromatograph. No such by‐products were observed when oleic acid was isomerized. Apparently some type of hydrogen‐transfer reaction accompanies thecis‐trans isomerization of polyunsaturated acids with selenium.
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