Abstract
Conformation of bicyclic guanidines with kappa-opioid receptor activity derived in our laboratory from a positional scanning synthetic combinatorial library is presented in this work. We propose a common bioactive conformation and putative pharmacophoric features by means of 3D similarity methods. Our 'Y' shape molecular binding model explains structure-activity relationships and suggests that the guanidine functionality and a 4-methoxybenzyl group may be involved in key interactions with the receptor. Comparison of our model with known opiates suggest a similar binding mode showing that the bicyclic guanidines presented in this work are suitable scaffolds for further development of new opioid receptors ligands.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Bridged Bicyclo Compounds, Heterocyclic / chemistry*
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Bridged Bicyclo Compounds, Heterocyclic / metabolism
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Combinatorial Chemistry Techniques
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Computational Biology
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Guanidine / analogs & derivatives*
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Guanidine / chemistry*
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Guanidine / metabolism
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Nucleic Acid Conformation*
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Receptors, Opioid / chemistry*
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Receptors, Opioid / metabolism
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Receptors, Opioid, delta / chemistry*
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Receptors, Opioid, delta / metabolism
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Receptors, Opioid, mu / chemistry*
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Receptors, Opioid, mu / metabolism
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Thermodynamics
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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Receptors, Opioid
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Receptors, Opioid, delta
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Receptors, Opioid, mu
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Guanidine