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Mar. Drugs 2010, 8(2), 235-254;

Natural Occurrence of 2′,5′-Linked Heteronucleotides in Marine Sponges

Department of Gene Technology, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia
Author to whom correspondence should be addressed.
Received: 23 December 2009 / Revised: 18 January 2010 / Accepted: 1 February 2010 / Published: 2 February 2010
(This article belongs to the Special Issue Enzymes from the Sea: Sources, Molecular Biology and Bioprocesses)
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2′,5′-oligoadenylate synthetases (OAS) as a component of mammalian interferon-induced antiviral enzymatic system catalyze the oligomerization of cellular ATP into 2′,5′-linked oligoadenylates (2-5A). Though vertebrate OASs have been characterized as 2′-nucleotidyl transferases under in vitro conditions, the natural occurrence of 2′,5′-oligonucleotides other than 2-5A has never been demonstrated. Here we have demonstrated that OASs from the marine sponges Thenea muricata and Chondrilla nucula are able to catalyze in vivo synthesis of 2-5A as well as the synthesis of a series 2′,5′-linked heteronucleotides which accompanied high levels of 2′,5′-diadenylates. In dephosphorylated perchloric acid extracts of the sponges, these heteronucleotides were identified as A2′p5′G, A2′p5′U, A2′p5′C, G2′p5′A and G2′p5′U. The natural occurrence of 2′-adenylated NAD+ was also detected. In vitro assays demonstrated that besides ATP, GTP was a good substrate for the sponge OAS, especially for OAS from C. nucula. Pyrimidine nucleotides UTP and CTP were also used as substrates for oligomerization, giving 2′,5′-linked homo-oligomers. These data refer to the substrate specificity of sponge OASs that is remarkably different from that of vertebrate OASs. Further studies of OASs from sponges may help to elucidate evolutionary and functional aspects of OASs as proteins of the nucleotidyltransferase family. View Full-Text
Keywords: 2′,5′-oligoadenylate synthetase; OAS; marine sponge; 2′,5′-linked heteronucleotides; natural products 2′,5′-oligoadenylate synthetase; OAS; marine sponge; 2′,5′-linked heteronucleotides; natural products
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Lopp, A.; Reintamm, T.; Kuusksalu, A.; Tammiste, I.; Pihlak, A.; Kelve, M. Natural Occurrence of 2′,5′-Linked Heteronucleotides in Marine Sponges. Mar. Drugs 2010, 8, 235-254.

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