Molecular simulation applied to 2-(N′-alkylidenehydrazino)- and 2-(N′-aralkylidenehydrazino)adenosine A2 agonists

Pp, Mager; Richter, Maik; Reinhardt, Robert M.

doi:10.1016/0223-5234(96)88205-5

Cited by 7 publications

(1 citation statement)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A 1 and A 3 adenosine receptor (AR) activation can lead to an inhibition of adenylate cyclase activity, while A 2A and A 2B AR activation causes a stimulation of adenylate cyclase [3]. On the basis of the amino acid sequence of the A 2A receptor different 3D models for the ligand binding site have been developed based on the low-energy conformations of the ligands [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

CoMFA Study on Adenosine A2A Receptor Agonists

Doytchinova¹,

Valkova

Natcheva

2001

Quant. Struct.-Act. Relat.

View full text Add to dashboard Cite

A step-wise CoMFA-based procedure was applied to a series of 51 C2-oxyadenosines in order to select the most predictive conformation for binding to A 2A adenosine receptor. The highest correlation and predictive power was found for conformers with the side chain at the 2-position oriented in the direction opposite to the exocyclic amino group on the adenine ring (torsion N1C2OR ¼ 120 ) and fully extended. The interaction of ligand and receptor is under steric and electrostatic control. The steric contribution is of greater importance for the predictivity than the electrostatic one. Hydrophobicity of the compounds investigated does not affect significantly either the affinity to A 2A adenosine receptor, nor the predictivity of the models.

show abstract

Section: Introductionmentioning

confidence: 99%

CoMFA Study on Adenosine A2A Receptor Agonists

Doytchinova¹,

Valkova

Natcheva

2001

Quant. Struct.-Act. Relat.

View full text Add to dashboard Cite

show abstract

Molecular modeling of adenosine receptors: new results and trends

Martinelli

Tuccinardi

2007

Medicinal Research Reviews

View full text Add to dashboard Cite

Adenosine is a ubiquitous neuromodulator, which carries out its biological task by stimulating four cell surface receptors (A(1), A(2A), A(2B), and A(3)). Adenosine receptors (ARs) are members of the superfamily of G protein-coupled receptors (GPCRs). Their discovery opened up new avenues for potential drug treatment of a variety of conditions such as asthma, neurodegenerative disorders, chronic inflammatory diseases, and many other physiopathological states that are believed to be associated with changes in adenosine levels. Knowledge of the 3D structure of ARs could be of great help in the task of understanding their function and in the rational design of specific ligands. However, since GPCRs are membrane-bound proteins, high-resolution structural characterization is still an extremely difficult task. For this reason, great importance has been placed on molecular modeling studies and, particularly in the last few years, on homology modeling (HM) techniques. The publication of the first high-resolution crystal structure for bovine rhodopsin (bRh), a GPCR superfamily member, provides the option of utilizing HM to generate 3D models based on detailed structural information. In this review we report, analyze, and compare the main experimental data, computational HM procedures and validation methods used for ARs, describing in detail the most successful results.

show abstract