A number of strains of Oidiodendron truncatum was shown to produce a new antibiotic, PR-1350, which was isolated in the form of an amorphous powder either directly or via a crystalline monomethanolate, PR-1381, which in solution is reconverted to the parent compound. The antibiotic inhibits a broad spectrum of Gram-positive and Gram-negative bacteria in vitro, and has been shown to be active against P-388 lymphocytic leukemia in mice. Biosynthetic considerations based on the results of [1-13C]acetate incorporation indicate that the antibiotic is a diterpene of the clerodane type.
The identity of the product obtained by sodium borohydride reduction of NAD § as 1,6-dihydro-NAD has been verified by 13C NMR spectroscopy. The behaviour of this compound during chromatography on Sephadex G-15 has been found identical with that of the humidity induced inhibitor detected in NADH preparations and postulated to be identical with 1,6-dihydro-NAD. Evidence is presented that this inhibitor is responsible for the bulk of the inhibitory effect developed in moist NADH preparations and that it is generated through a bimolecular reaction between NADH and NAD + which in essence is a NAD + catalyzed double bond rearrangement of NADH effected by transfer of hydride anions from NADH to NAD + . One implication of these findings, that removal of NAD + from NADH preparations should convey increased stability to the reduced cofactor, has been verified. The structure of the lactate dehydrogenase inhibitors described in the literature is discussed.Abbreviations: NADH = 1,4-dihydro-nicotinamide adenine dinucleotide, LDH = lactate dehydrogenase, ADPR = adenosine 5'-diphosphoribose, NAD + = nicotinamide adenine dinucleotide, 1,6-dihydro-NAD = 1,6-dihydronicotinamide adenine dinucleotide, TMS = tetramethyl silane, compound 2 = 4-phosphoryloxy-1,4-dihydro-nicotinamide adenine dinucleotide.
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