2q6j: Difference between revisions
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New page: left|200px<br /> <applet load="2q6j" size="450" color="white" frame="true" align="right" spinBox="true" caption="2q6j, resolution 2.700Å" /> '''Crystal Structure ... |
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[[Image:2q6j.gif|left|200px]]<br /> | [[Image:2q6j.gif|left|200px]]<br /><applet load="2q6j" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2q6j" size=" | |||
caption="2q6j, resolution 2.700Å" /> | caption="2q6j, resolution 2.700Å" /> | ||
'''Crystal Structure of Estrogen Receptor alpha Complexed to a B-N Substituted Ligand'''<br /> | '''Crystal Structure of Estrogen Receptor alpha Complexed to a B-N Substituted Ligand'''<br /> | ||
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==Overview== | ==Overview== | ||
To increase the chemical diversity of bioactive molecules by incorporating, unusual elements, we have examined the replacement of a C=C double bond, with the isoelectronic, isostructural B-N bond in the context of, nonsteroidal estrogen receptor (ER) ligands. While the B-N bond was, hydrolytically labile in the unhindered cyclofenil system, the more, hindered anilino dimesitylboranes, analogs of triarylethylene estrogens, were easily prepared, hydrolytically stable, and demonstrated substantial, affinity for ERs. X-ray analysis of one ERalpha-ligand complex revealed, steric clashes with the para methyl groups distorting the receptor;, removal of these groups resulted in an increase in affinity, potency, and, transcriptional efficacy. These studies define the structural determinants, of stability and cellular bioactivity of a B-N for C=C substitution in, nonsteroidal estrogens and provide a framework for further exploration of, "elemental isomerism" for diversification of drug-like molecules. | To increase the chemical diversity of bioactive molecules by incorporating, unusual elements, we have examined the replacement of a C=C double bond, with the isoelectronic, isostructural B-N bond in the context of, nonsteroidal estrogen receptor (ER) ligands. While the B-N bond was, hydrolytically labile in the unhindered cyclofenil system, the more, hindered anilino dimesitylboranes, analogs of triarylethylene estrogens, were easily prepared, hydrolytically stable, and demonstrated substantial, affinity for ERs. X-ray analysis of one ERalpha-ligand complex revealed, steric clashes with the para methyl groups distorting the receptor;, removal of these groups resulted in an increase in affinity, potency, and, transcriptional efficacy. These studies define the structural determinants, of stability and cellular bioactivity of a B-N for C=C substitution in, nonsteroidal estrogens and provide a framework for further exploration of, "elemental isomerism" for diversification of drug-like molecules. | ||
==About this Structure== | ==About this Structure== | ||
2Q6J is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with A48 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 2Q6J is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=A48:'>A48</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q6J OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:29:54 2008'' | ||
