3-Deazaadenosine analogues of p5′A2′p5′A2′p5′A: synthesis, stereochemistry, and the roles of adenine ring nitrogen-3 in the interaction with RNase L

Kalinichenko, Еlena N.; Podkopaeva, T. L.; Budko, Elena V; Seela, Frank; Dong, Bin; Silverman, Robert H.; Vepsäläinen, Jouko; Torrence, Paul F.; Mikhailopulo, Igor A.

doi:10.1016/j.bmc.2004.04.021

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…Substitution of the adenosine moiety with 1-deazaadenosine (c 1 A) or 3-deazaadenosine (c 3 A) at different positions of the 2-5A chain first allowed to establish the role played by each of the adenine heterocycle nitrogen atoms in RNase L binding and activation [20][21][22].…”

Section: (2′-5′)oligoadenylates Modified On the Heterocyclic Basementioning

confidence: 99%

“…It was shown that substitution of 5′-terminal or 2′-terminal adenosine for c 3 A produced respective analogs including p5′(c 3 A)2′p5′A2′p5′A and p5′A2′p5′A2′p5′(c 3 A) which were not inferior to the parent tetramer in activating RNase L (EC 50 ≤ 1 nM) [22]. In contrast, p5′A2′p5′(c 3 A)2′p5′A showed a reduced ability to activate RNase L (EC 50 ≤ 10 nM).…”

Section: Structural Formulas Of Adenosine (A) 1-dezazaadenosine (C 1 ...mentioning

confidence: 99%

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Modified (2′,5′)Oligonucleotides: The Influence of Structural and Steriochemical Factors on Biological and Immunotropic Activity

Kalinichenko¹

2023

Oligonucleotides - Overview and Applications

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The synthesis of a large number of analogs of natural 2-5A and the results of studies to clarify the relationship between the structure and spatial organization (stereochemistry) and the biological properties of analogs 2-5A have convincingly demonstrated that by changing the structure and/or stereochemistry of molecules, it is possible to achieve either strengthening of known properties or giving new ones. The replacement of the adenosine fragment with 1-deazaadenosine (c1A) or 3-deazaadenosine (c3A) at various positions of the 2-5A chain demonstrated the role of each of the nitrogen atoms of the adenine heterocycle in the processes of binding and activation of RNase L. The use of conformationally rigid fluorodeoxyadenylates in enzymatic reactions made it possible to differentiate the role of structural and stereochemical factors and demonstrate the influence of molecules’ stereochemistry on their biological properties. Oligomers with ribo-[(2′,5′)A2ARA] and lixo-[(2′,5′)A2ALA] conformation in the (A3) terminal fragment showed activity against diseases associated with disorders of T-cell immunity, autoimmune diseases, viral infections, lymphocytic malignant transformations, prevention of transplant rejection after bone marrow transplantation and, possibly, in the treatment of complications associated with the reaction of the transplanted tissue and the recipient’s tissue.

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Section: (2′-5′)oligoadenylates Modified On the Heterocyclic Basementioning

confidence: 99%

Section: Structural Formulas Of Adenosine (A) 1-dezazaadenosine (C 1 ...mentioning

confidence: 99%

Modified (2′,5′)Oligonucleotides: The Influence of Structural and Steriochemical Factors on Biological and Immunotropic Activity

Kalinichenko¹

2023

Oligonucleotides - Overview and Applications

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“…From 1970 in Laboratory of Nucleotides and Polynucleotides of Institute of Bioorganic chemistry NAS of Belarus complex study of chemistry, biochemistry and biotechnology of nucleonic acids components is carrying out. As a result of investigations new highly effective methods for synthesis of different analogs of nucleosides, nucleotides and olygonucleotides have been proposed for application both in medicine and agriculture [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Nucleosides`s Analogues and their Application as Chemotherapeutic Agents

Kalinichenko

2013

Eur Chem Tech J

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Application of the chemical-enzyme approach which is a combination of chemical synthesis and enzyme reaction has allowed to develop original effective methods of synthesis both new compounds and known nucleoside antibiotics which have been inaccessible earlier. Among them preparations for the treatment of oncohaematological diseases like: Cytarabin, Leukladin (Cladribine), Fludarabel, ara-adenosine (Vidarabine), ara-guanosine and produced from the last by chemical method a new medicine for the treatment of T-cellular lymphomas – Nelarabine. Results on the comparative study of antileukemic activity of purine nucleosides using the model of the lymphoid leukemia L1210 are presented. It is shown that the model of mouse lymphoid leukemia L1210 in vivo is not useful for results extrapolation for human if specific activity of modified nucleoside shows itself in therapy of hair-cellular leucosis (HCL), acute myeloid leukemia (AML) and especially for T-cellular leucosis. From commercially available derivative of 2'-fluoro-arabinofuranose developed an original method for the synthesis of antitumor drug Clofarabine for treatment of acute lymphoblastic leukaemia (ALL) in pediatric patients. Highly effective technology producing pharmaceutical substance Pemetrexed has been developed. At present new chemical-therapeutic agent Pemetrexed, which is structural analog of folic acid containing 7-deasaguanine is introduced into clinic practice. It is first agent specially developed for treatment of malignant pleural mesothelioma. It is worth to note that possibilities of the Pemetrexed’s usage for treatment of other tumor diseases are not exhausted still. It is interesting to develop new method of synthesis of modified pyrimidine nucleoside Azacytidine possesses both cytostatic action and ability to inhibit DNA methyltransferases.

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“…2-5A an a logues with chem i cal mod i fi ca tions, in clud ing those that in crease the nuclease re sis tance, of ten re veal higher bi o log i cal activ ity. A broad va ri ety of 2-5A an a logues with mod ified car bo hy drate res i dues, internucleotide phos phates, and heterocyclic bases has been ob tained [1,2,[6][7][8][9][10][11][12]. Thus, triadenylate 1b mod i fied with epoxyadenosine is known to be the in hib i tor of post-trans plan ta tion tis sue re jec tion [12] and was shown to pos sess cardioprotecting fea tures [13].…”

mentioning

confidence: 99%

Synthesis of (2'-5')-triadenylate and their analogues using O-nucleophilic catalysis of internucleotide coupling reaction

Dubey

2007

Biopolym. Cell

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2¢-5¢)-triadenylate and its an a logues con tain ing 3¢-ter mi nal epoxyadenosine or cordycepin res i due were ob tained by phosphotriester ap proach in the pres ence of 4-ethoxypyridine N-ox ide (EPO) as O-nucleophilic cat a lyst of cou pling re ac tion. The cou pling re ac tions pro ceeded with high speed (be low 5 min) and ef ficiency (yield 86-92%). The re ac tion yields achieved in the pres ence of N-methylimidazole were sub stantially lower (80-85%), and the fi nal yields of triadenylates were only 21-25%, as com pared to 29-35% ob tained with N-ox ide.

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3-Deazaadenosine analogues of p5′A2′p5′A2′p5′A: synthesis, stereochemistry, and the roles of adenine ring nitrogen-3 in the interaction with RNase L

Cited by 6 publications

References 30 publications

Modified (2′,5′)Oligonucleotides: The Influence of Structural and Steriochemical Factors on Biological and Immunotropic Activity

Modified (2′,5′)Oligonucleotides: The Influence of Structural and Steriochemical Factors on Biological and Immunotropic Activity

Synthesis of Nucleosides`s Analogues and their Application as Chemotherapeutic Agents

Synthesis of (2'-5')-triadenylate and their analogues using O-nucleophilic catalysis of internucleotide coupling reaction

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