Structural and enzymic properties of adenine 1-oxide nucleotides

Abstract

We decribed the preparation of adenine 1-oxide nucleotides by oxidation of the natural compounds with monopermaleic acid in aqueous solutions at neutral pH, with an overall yield after chromatographic purification between 75 and 80%. If irradiated, the adenine 1-oxide nucleotides undergo a photochemical rearrangement reaction, the main photoproducts in aqueous solution at alkaline pH being the corresponding isoguanine nucleotides. The modified ring vibration pattern of the 1-oxide analogues as well as the 13C chemical shift indicate a loss of aromaticity as compared to the natural compounds. Coupling constant measurements show that the dihedral angle between the 31POC and OC13C planes is around 180degree, i.e., trans, as in the natural adenine nucleotides. The modified adenine nucleotides were tested as potential substrates and/or inhibitors of mitochondrial processes, as substrates of varous phosphotransferases from mitochondria or cytosol, and as allosteric effectors in the reactions catalyzed by glutamate dehydrogenase and phosphofructokinase. Although the adenine 1-oxide nucleotides are not recognized by the translocase system of the inner mitochondrial membrane, they are good substrates for mitochondrial phosphotransferases located in the intermembrane space. Similarly, they participate in the phosphoryl group transfer reactions catalyzed by pyruvate kinase, phosphofructokinase, and hexokinase. As allosteric effectors, the modified nucleotides are less active than the natural compounds, probably because of a lower binding capacity to the allosteric sites of the regulatory enzymes.

Interaction of sulfur‐containing ATP analogs with rabbit muscle phosphofructokinase

“…o'ITP was prepared by oxidative deammatlon of adenosine-1 -oxide 5'.triphosphate [7,8]. Other natural or modified nucleotides, enzymes and substrates were supplied by Boehringer Mannheim.…”

The development of isoguanosine: from discovery, synthesis, and modification to supramolecular structures and potential applications

“…In 1975, Mantsch 41 et al reported that isoguanine nucleotides are not recognized by the mitochondrial endometrial translocation enzyme system, but they can be well recognized by mitochondrial phosphatases in the inter-membrane space. They are also involved in phosphoryl group transfer reactions.…”

“…196 And in 1974, Holy 197 et al reported that isoG can also inhibit inducible E. coli binding site. In addition, in 1975, Mantsch 41 et al reported that its 5 0 -di-and -tri-phosphates can strongly bind and inhibit glutamic acid dehydrogenase. In 1988, Wissler 198 et al reported that isoG also acts as an essential constituent of Cu(II)-containing ribonucleic acid produced by cultured pig macrophages.…”

“…The other product is isoG via the rearrangement of oxygen atom to the neighboring carbon atom. Subsequently in 1975, Mantsch 41 et al concluded that if nucleotides of the initial substance 2 is irradiated with UV light under alkaline condition (0.01 M NH 4 OH), isoG nucleotides can be the corresponding primary products. This is also the case for adenine 1-oxide (10, Fig.…”

Σύνθεση Ομονουκλεοζιτικών Παραγώγων Και Ετεροκυκλικών Παραγώγων Πουρινών Με Πιθανό Βιολογικό Ενδιαφέρον

“…Μαζί με την 2΄-αμινογουανοσίνη,83 η ισογουανοσίνη είναι ο μόνος γνωστός φυσικός νουκλεοζίτης γουανίνης που δρα ως αντιβιοτικό. Οι διφωσφορικοί και τριφωσφορικοί εστέρες της ισογουανοσίνης είναι ισχυροί αναστολείς της αφυδρογονάσης του γλουταμινικού οξέος 84. Η σύνθεση της μπορεί να γίνει εύκολα από φωτοϊσομερίωση του 1-οξειδίου της αδενοσίνης (68) 84.…”