Multiple Fragment Docking and Linking in Primary and Secondary Pockets of Dopamine Receptors
ACS Medicinal Chemistry Letters2014Vol. 5(9), pp. 1010–1014
Citations Over TimeTop 12% of 2014 papers
Abstract
A sequential docking methodology was applied to computationally predict starting points for fragment linking using the human dopamine D3 receptor crystal structure and a human dopamine D2 receptor homology model. Two focused fragment libraries were docked in the primary and secondary binding sites, and best fragment combinations were enumerated. Similar top scoring fragments were found for the primary site, while secondary site fragments were predicted to convey selectivity. Three linked compounds were synthesized that had 9-, 39-, and 55-fold selectivity in favor of D3 and the subtype selectivity of the compounds was assessed on a structural basis.
Related Papers
- → Differential visualization of dopamine D2 and D3 receptors in rat brain(1993)23 cited
- → The dopamine D3 receptor and schizophrenia: pharmacological, anatomical and genetic approaches(1995)44 cited
- → Dopamine D2/D3 receptor agonists produce antidepressant‐like effects in the rat forced swim test through co‐activation of both receptor subtypes(2008)1 cited
- → DOPAMINE D1, D2, D3, D4 RECEPTOR GENE POLYMORPHISMS AND SCHIZOPHRENIA(1992)
- → Dopamine D2 receptor; dopamine D3 receptor(2012)