Publicaciones 2011-2020

@article{hugo2017functional,
title = {Functional Roles of T3.37 and S5.46 in the Activation Mechanism of the Dopamine D1 Receptor},
author = { E.A. Hugo and B.K. Cassels and A. Fierro},
url = {/brokenurl#<Go to ISI>://WOS:000399406500014},
doi = {10.1007/s00894-017-3313-0},
issn = {1610-2940},
year = {2017},
date = {2017-01-01},
journal = {Journal of Molecular Modeling},
volume = {23},
number = {4},
abstract = {The activation mechanism of dopamine receptors is unknown. The amino acids S5.42, S5.43, and S5.46 located in helix 5 appear to be crucial, but their specific roles in receptor activation have not been studied. We modeled the D1 dopamine receptor using the crystal structures of the D3 dopamine and beta 2 adrenergic receptors. Molecular dynamics simulations show that the interaction of dopamine with the D1 receptor leads to the formation of a hydrogen-bond network with its catechol group and helices 3, 5, and 6, including water molecules. The para hydroxyl group of dopamine binds directly to S5.42 and N6.55, the latter also interacting with S5.43. Unexpectedly, S5.46 does not interact directly with the catechol; instead, it interacts through a water molecule with S5.42 and directly with T3.37. The formation of this hydrogen-bond network, part of which was previously observed in docking studies with dopamine agonists, triggers the opening of the E6.30-R3.60 ionic lock associated with the activation of GPCRs. These changes do not occur in the unbonded (apo) receptor or when it is in a complex with the antagonist 3-methoxy- 5,6,7,8,9,14-hexahydrodibenz[d, g]azecine. Our results provide valuable insight into the T3.37-S5.46-water-S5.43-ligand interaction, which may be crucial to the activation of the D1 dopamine receptor and should be considered during the design of novel agonists.},
keywords = {crystal-structure, d-1, d1 dopamine dopamine, dynamics, identification, interactions, models, molecular pharmacophore, receptor, recognition residues, s5.46, serine structures},
pubstate = {published},
tppubtype = {article}
}

@article{RN191,
title = {Synthesis of N-(Halogenated) Benzyl Analogs of Superpotent Serotonin Ligands},
author = { C. Tirapegui and M.A. Toro-Sazo and B.K. Cassels},
url = {/brokenurl#<Go to ISI>://WOS:000347833800022},
doi = {10.4067/S0717-97072014000300022},
issn = {0717-9707},
year = {2014},
date = {2014-01-01},
journal = {Journal of the Chilean Chemical Society},
volume = {59},
number = {3},
pages = {2625-2627},
abstract = {In the last four years a group of extremely potent designer drugs, the N-benzylated phenylethylamines known as the NBOMe series, has surfaced on the street and in the news media. Although data documenting their high affinity and preference for 5-HT2 serotonin receptors abound (5-HT2A receptor activation is generally associated with the action of the "classical" hallucinogens), relatively little is known about the molecular basis of their potency and selectivity. In the setting of a project aiming to evaluate the possible involvement of halogen bonds in the binding of monoaminergic ligands to their receptors, we have begun to synthesize halogenated derivatives of known N-benzylated compounds for their pharmacological study. Here we report the synthesis of new phenylethylamine and tryptamine derivatives incorporating bromine atoms in their N-benzyl moiety.},
keywords = {n-benzylphenylethylamine, n-benzyltryptamine, receptor, synthesis},
pubstate = {published},
tppubtype = {article}
}