8-Aminoadenine

8-Aminoadenine is an agonist of adenine receptor with Ki value of 0.0341 μM [1].

Adenine receptor is a G protein-coupled receptor activated by the nucleoside adenosine. There are four types of adenosine receptors: A1, A2A, A2B and A3. A1 and A2A receptors play an important role in the heart, regulating coronary blood flow and myocardial oxygen consumption. A2B and A3 receptors are involved in inflammation and immune responses.

8-Aminoadenine is an adenine receptor agonist with Ki values of 0.0341 and 6.51 μM for human and rat, respectively. In HEK293 cell membrane, 8-Aminoadenine was more potent than adenine (Ki = 0.0471 μM) and exhibited 190-fold more potent than the rat binding site. In 1321N1 astrocytoma cells expressing the rAde1R, 8-Aminoadenine (500 μM) inhibited isoproterenol-stimulated cAMP accumulation, which suggested that 8-Aminoadenine inhibited adenine uptake [1].

Reference:
[1].  Borrmann T, Abdelrahman A, Volpini R, et al. Structure-activity relationships of adenine and deazaadenine derivatives as ligands for adenine receptors, a new purinergic receptor family. J Med Chem, 2009, 52(19): 5974-5989.

Property editing of peptide nucleic acids (PNA): gem-dimethyl, cyanuryl and 8-aminoadenine PNAs.[Pubmed:18029564]

Nucleic Acids Symp Ser (Oxf). 2007;(51):17-8.

We herein describe the introduction of gem-dimethyl substitution into the aminoethylglycyl backbone of PNA to impart steric constraint and pre-organise PNA for selective recognition of nucleic acids. Introduction of cyanuric acid and 8-Aminoadenine as pyrimidine and purine analogs that can form base pairing from either face is also described to overcome the rotameric problems in PNA sidechain orientations and thereby enhance the statistical probability for base pairing. The UV-thermal melting studies of the derived triplexes with complementary DNA provide support for this rationale.

Structure-activity relationships of adenine and deazaadenine derivatives as ligands for adenine receptors, a new purinergic receptor family.[Pubmed:19731917]

J Med Chem. 2009 Oct 8;52(19):5974-89.

Adenine derivatives bearing substituents in the 2-, N(6)-, 7-, 8-, and/or 9-position and a series of deazapurines were synthesized and investigated in [(3)H]adenine binding studies at the adenine receptor in rat brain cortical membrane preparations (rAde1R). Steep structure-activity relationships were observed. Substitution in the 8-position (amino, dimethylamino, piperidinyl, piperazinyl) or in the 9-position (2-morpholinoethyl) with basic residues or introduction of polar substituents at the 6-amino function (hydroxy, amino, acetyl) represented the best modifications. Functional evaluation of selected adenine derivatives in adenylate cyclase assays at 1321N1 astrocytoma cells stably expressing the rAde1R showed that all compounds investigated were agonists or partial agonists. A subset of compounds was additionally investigated in binding studies at human embryonic kidney (HEK293) cells, which also express a high-affinity adenine binding site. Structure-affinity relationships at the human cell line were similar to those at the rAde1R, but not identical. In particular, N(6)-acetyladenine (25, K(i) rat: 2.85 microM; K(i) human: 0.515 microM) and 8-Aminoadenine (33, K(i) rat: 6.51 microM; K(i) human: 0.0341 microM) were much more potent at the human as compared to the rat binding site. The new AdeR ligands may serve as lead structures and contribute to the elucidation of the functions of the adenine receptor family.