Computational modelling of interaction between isovaltrate and adenosine A1 eceptor


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Abstract

Isovaltrate, a valepotriate contained in valerian roots, is an inverse agonist of adenosine Ai receptor with micromolar affinity. Here, we present results of molecular modelling of its binding to this receptor by flexible docking with Galaxy7TM web server. We modelled isovaltrate binding to human and rat adenosine A1 receptor. The modelling has shown that isovaltrate mimics xanthine antagonists upon binding to adenosine A1 receptor. It occupies similar position and forms analogous interactions: hydrogen bond with Asn254 and hydrophobic contacts with Phe171, Leu250, Ile274. Despite lacking aromatic structure, bicyclic core formed vast hydrophobic interactions with Phe171 positioning itself similar to xanthine and flavonoid core. Other studied valepotriates, valtrate and deacetylisovaltrate, were unabe to fully mimic there interactions. We proposed that xanthine, flavonoid and isovaltrate binding is provided by common structural features: flat or almost flat bicyclic core, hydrogen bond acceptor attached to it and side chains. Obtained modelling data can be used for designing new adenosine receptor blockers and sedative drugs.

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About the authors

G. F Kurakin

Tver State Medical University

Email: phyzyk@mail.ru
Resident, Department of Biochemistry and Laboratory Medicine Tver

N. P Lopina

Tver State Medical University

Ph.D. (Chem.), Associate Professor, Department of Chemistry Tver

G. E Bordina

Tver State Medical University

Ph.D. (Biol.), Associate Professor, Department of Chemistry Tver

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