scholarly journals Design and Synthesis of 2,6-Disubstituted-4′-Selenoadenosine-5′-N,N-Dimethyluronamide Derivatives as Human A3 Adenosine Receptor Antagonists

2021 ◽  
Vol 14 (4) ◽  
pp. 363
Author(s):  
Hongseok Choi ◽  
Kenneth A. Jacobson ◽  
Jinha Yu ◽  
Lak Shin Jeong
Keyword(s):  
Binding Affinity ◽  
Adenosine Receptor ◽  
Functional Assay ◽  
Antagonist Activity ◽  
Methyl Group ◽  
Design And Synthesis ◽  
Selective Antagonists ◽  
A3 Adenosine Receptor ◽  
High Binding Affinity

A new series of 4′-selenoadenosine-5′-N,N-dimethyluronamide derivatives as highly potent and selective human A3 adenosine receptor (hA3AR) antagonists, is described. The highly selective A3AR agonists, 4′-selenoadenosine-5′-N-methyluronamides were successfully converted into selective antagonists by adding a second N-methyl group to the 5′-uronamide position. All the synthesized compounds showed medium to high binding affinity at the hA3AR. Among the synthesized compounds, 2-H-N6-3-iodobenzylamine derivative 9f exhibited the highest binding affinity at hA3AR. (Ki = 22.7 nM). The 2-H analogues generally showed better binding affinity than the 2-Cl analogues. The cAMP functional assay with 2-Cl-N6-3-iodobenzylamine derivative 9l demonstrated hA3AR antagonist activity. A molecular modelling study suggests an important role of the hydrogen of 5′-uronamide as an essential hydrogen bonding donor for hA3AR activation.

scholarly journals Synthesis of 3′-ureidoadenosines and their high binding affinity at the mutant A3 adenosine receptor

2005 ◽  
Vol 49 (1) ◽  
pp. 105-106 ◽  
Author(s):  
Ae Yil Kim ◽  
Hea Ok Kim ◽  
Myoung Jung Kim ◽  
Moon Woo Chun ◽  
Kang Man Lee ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Adenosine Receptor ◽  
High Binding ◽  
A3 Adenosine Receptor ◽  
High Binding Affinity

ChemInform Abstract: Synthesis of 3′-(Ureido)adenosine Derivatives and Their High Binding Affinity at the Mutant A3 Adenosine Receptor

ChemInform ◽  
2008 ◽  
Vol 39 (29) ◽  
Author(s):  
Ae Yil Kim ◽  
Hea Ok Kim ◽  
Myoung Jung Kim ◽  
Moon Woo Chun ◽  
Kang Man Lee ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Adenosine Receptor ◽  
High Binding ◽  
A3 Adenosine Receptor ◽  
Adenosine Derivatives ◽  
High Binding Affinity

scholarly journals RNA binding to human METTL3-METTL14 restricts N6-deoxyadenosine methylation of DNA in vitro

2022 ◽  
Author(s):  
Shan Qi ◽  
Javier Mota ◽  
Siu-Hong Chan ◽  
Johanna Villarreal ◽  
Nan Dai ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Rna Binding ◽  
Methyl Group ◽  
High Affinity ◽  
Methylation Of Dna ◽  
Dna And Rna ◽  
Close Proximity ◽  
Methylation Activity

Methyltransferase like-3 (METTL3) and METTL14 complex transfers a methyl group from S-adenosyl-L-methionine to N6 amino group of adenosine bases in RNA (m6A) and DNA (m6dA). Emerging evidence highlights a role of METTL3-METTL14 in the chromatin context, especially in processes where DNA and RNA are held in close proximity. However, a mechanistic framework about specificity for substrate RNA/DNA and their interrelationship remain unclear. By systematically studying methylation activity and binding affinity to a number of DNA and RNA oligos with different propensities to form inter- or intra-molecular duplexes or single-stranded molecules in vitro, we uncover an inverse relationship for substrate binding and methylation and show that METTL3-METTL14 preferentially catalyzes the formation of m6dA in single-stranded DNA (ssDNA), despite weaker binding affinity to DNA. In contrast, it binds structured RNAs with high affinity, but methylates the target adenosine in RNA (m6A) much less efficiently than it does in ssDNA. We also show that METTL3-METTL14-mediated methylation of DNA is largely restricted by structured RNA elements prevalent in long noncoding and other cellular RNAs.

scholarly journals Role of Mast Cell-Derived Adenosine in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 2603 ◽  
Author(s):  
Yaara Gorzalczany ◽  
Ronit Sagi-Eisenberg
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Inflammatory Mediators ◽  
Adenosine Receptor ◽  
Tumor Development ◽  
A3 Adenosine Receptor

Accumulating evidence has highlighted the accumulation of mast cells (MCs) in tumors. However, their impact on tumor development remained controversial. Indeed, cumulative data indicate an enigmatic role for MCs in cancer, whereby depending on the circumstances, which still need to be resolved, MCs function to promote or restrict tumor growth. By responding to multiple stimuli MCs release multiple inflammatory mediators, that contribute to the resolution of infection and resistance to envenomation, but also have the potency to promote or inhibit malignancy. Thus, MCs seem to possess the power to define tumor projections. Given this remarkable plasticity of MC responsiveness, there is an urgent need of understanding how MCs are activated in the tumor microenvironment (TME). We have recently reported on the direct activation of MCs upon contact with cancer cells by a mechanism involving an autocrine formation of adenosine and signaling by the A3 adenosine receptor. Here we summarized the evidence on the role of adenosine signaling in cancer, in MC mediated inflammation and in the MC-cancer crosstalk.

SYNTHESIS OF 3′-UREIDOADENOSINE ANALOGUES AND THEIR BINDING AFFINITY TO THE A3 ADENOSINE RECEPTOR

2005 ◽  
Vol 24 (5-7) ◽  
pp. 1119-1121 ◽  
Author(s):  
Moon Woo Chun ◽  
Hyouk Woo Lee ◽  
Ae Yil Kim ◽  
Myong Jung Kim ◽  
Hea Ok Kim ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Adenosine Receptor ◽  
A3 Adenosine Receptor

ChemInform Abstract: Introduction of Alkynyl Chains on C-8 of Adenosine Led to Very Selective Antagonists of the A3 Adenosine Receptor.

ChemInform ◽  
2010 ◽  
Vol 32 (46) ◽  
pp. no-no ◽  
Author(s):  
Rosaria Volpini ◽  
Stefano Costanzi ◽  
Catia Lambertucci ◽  
Sauro Vittori ◽  
K.-N. Klotz ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Selective Antagonists ◽  
A3 Adenosine Receptor

scholarly journals Design and Synthesis of Truncated 4'-Thioadenosine Derivatives as Potent and Selective A3 Adenosine Receptor Antagonists

2008 ◽  
Vol 52 (1) ◽  
pp. 641-642 ◽  
Author(s):  
X. Hou ◽  
S. Pal ◽  
W. J. Choi ◽  
H. O. Kim ◽  
A. Tipnis ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Receptor Antagonists ◽  
Design And Synthesis ◽  
A3 Adenosine Receptor
Sign in / Sign up

Export Citation Format

Share Document