7331-13-7Relevant academic research and scientific papers
Effect of phosphate activating group on oligonucleotide formation on montmorillonite: The regioselective formation of 3′,5′-linked oligoadenylates
Prabahar, K. Joseph,Cole, Timothy D.,Ferris, James P.
, p. 10914 - 10920 (1994)
The effects of amine structure on the montmorillonite-catalyzed oligomerization of the 5′-phosphoramidates of adenosine are investigated. 4-Aminopyridine derivatives yielded oligoadenylates as long as dodecamers with a regioselectivity for 3′,5′-phosphodiester bond formation averaging 88%. Linear and cyclic oligomers are obtained and no A5′ppA-containing products are detected. Oligomers as long as the hexanucleotide are obtained using 2-aminobenzimidazole as the activating group. A predominance of pA2′pA is detected in the dimer fraction along with cyclic 3′,5′-trimer; no A5′ppA-containing oligomers were detected. Little or no oligomer formation was observed when morpholine, piperidine, pyrazole, 1,2,4-triazole, and 2-pyridone are used as phosphate-activating groups. The effects of the structure of the phosphate activating group on the oligomer structure and chain lengths are discussed.
5′-β,γ-CHF-ATP Diastereomers: Synthesis and Fluorine-Mediated Selective Binding by c-Src Protein Kinase
Hwang, Candy S.,Kung, Alvin,Kashemirov, Boris A.,Zhang, Chao,McKenna, Charles E.
supporting information, p. 1624 - 1627 (2015/04/14)
The first preparation of the individual β,γ-CHF-ATP stereoisomers 12a and 12b is reported. Configurationally differing solely by the orientation of the C-F fluorine, 12a and 12b have discrete 31P (202 MHz, pH 10.9, ΔδPα 6 Hz, ΔδPβ 4 Hz) and 19F NMR (470 MHz, pH 9.8, ΔδF 25 Hz) spectral signatures and exhibit a 6-fold difference in IC50 values for c-Src kinase, attributed to a unique interaction of the (S)-fluorine of bound 12b with R388 in the active site.
Structure-activity relationship of adenosine 5′-diphosphoribose at the transient receptor potential melastatin 2 (TRPM2) channel: Rational design of antagonists
Moreau, Christelle,Kirchberger, Tanja,Swarbrick, Joanna M.,Bartlett, Stephen J.,Fliegert, Ralf,Yorgan, Timur,Bauche, Andreas,Harneit, Angelika,Guse, Andreas H.,Potter, Barry V. L.
supporting information, p. 10079 - 10102 (2014/01/17)
Adenosine 5′-diphosphoribose (ADPR) activates TRPM2, a Ca 2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure-activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2′-deoxy-ADPR (86, IC50 = 3 μM), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfamate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
Rapid synthesis of Abelson tyrosine kinase inhibitors using click chemistry
Kalesh, Karunakaran A.,Liu, Kai,Yao, Shao Q.
experimental part, p. 5129 - 5136 (2010/04/04)
Protein kinases catalyze the phosphorylation of serine, threonine, tyrosine and histidine residues in proteins. Aberrant regulation of kinase activity has been implicated in many diseases including cancer. Thus development of new strategies for kinase inhibitor design remains an active area of research with direct relevance to drug development. Abelson (Abl) tyrosine kinase is one of the Src-family of tyrosine kinases and is directly implicated in Chronic Myelogenous Leukemia (CML). In this article, we have, for the first time, developed an efficient method for the construction of small molecule-based bisubstrate inhibitors of Abl kinase using click chemistry. Subsequent biochemical screenings revealed a set of moderately potent inhibitors, a few of which have comparable potency to Imatinib (an FDA-approved drug for treatment of chronic myeloid leukemia) against Abl.
Phosphorodiamides as prodrugs for antiviral nucleosides
Shipitsyn, Alexander V.,Zakirova, Natalya F.,Belanov, Evgeny F.,Pronyaeva, Tatyana R.,Fedyuk, Nina V.,Kukhanova, Marina K.,Pokrovsky, Andrey G.
, p. 963 - 966 (2007/10/03)
New phosphorodiamides of modified nucleoside monophosphates were synthesized and their antiviral properties were evaluated.
