Sandbox Reserved 1723: Difference between revisions

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[[Image:Zinc_and_drugs_snip.PNG|450px|right|thumb|'''Figure 6''': Structures of (R)-Zinc-3573, Dextromethorphan, Morphine, and Codeine. The blue circles indicate conserved basic N-dimethyl group and the green squares show the conserved benzene rings.<ref name="Cao"/>]]

MRGPRX2 activation is associated with chronic itching or anaphylaxis reactions, a common side effect of many prescribed medications. <ref name="Cao"/> Among these drugs are opiods [https://en.wikipedia.org/wiki/Morphine morphine] and [https://en.wikipedia.org/wiki/Codeine codeine] and [https://en.wikipedia.org/wiki/Dextromethorphan dextromethorphan]. By analyzing the structures of these drugs, it can be seen that they contain chemical features similar to <scene name='90/904328/Zizwithaa/5'>agonist R-Zinc-3573</scene> (see Figure 6). They contain a conserved benzene ring that stabilizes them in binding pocket one (~~See~~ Figure 6). Similarly, they contain an N-dimethyl group that would allow them to form key bonds with residues Asp-184 and Glu-164. Lastly, these drugs have a similar shape and size to that of the agonist R-Zinc-3573.<ref name="Babina"> Babina, M., et al. "MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through β-Arrestin and Lack of Correlation with the FcεRI Pathway." Journal of Investigative Dermatology, 141(6), 1286-1296. https://doi.org/10.1016/j.jid.2020.09.017</ref> These structural and chemical similarities indicate the possibility of a similar binding mechanism.

MRGPRX2 activation is associated with chronic itching or anaphylaxis reactions, a common side effect of many prescribed medications. <ref name="Cao"/> Among these drugs are opiods [https://en.wikipedia.org/wiki/Morphine morphine] and [https://en.wikipedia.org/wiki/Codeine codeine] and [https://en.wikipedia.org/wiki/Dextromethorphan dextromethorphan]. By analyzing the structures of these drugs, it can be seen that they contain chemical features similar to <scene name='90/904328/Zizwithaa/5'>agonist R-Zinc-3573</scene> (see Figure 6). They contain a conserved benzene ring that stabilizes them in binding pocket one (see Figure 6). Similarly, they contain an N-dimethyl group that would allow them to form key bonds with residues Asp-184 and Glu-164. Lastly, these drugs have a similar shape and size to that of the agonist R-Zinc-3573.<ref name="Babina"> Babina, M., et al. "MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through β-Arrestin and Lack of Correlation with the FcεRI Pathway." Journal of Investigative Dermatology, 141(6), 1286-1296. https://doi.org/10.1016/j.jid.2020.09.017</ref> These structural and chemical similarities indicate the possibility of a similar binding mechanism.

This receptor is shallow and is able to bind to a variety of drugs, creating a need a solution to mediate the effects of MRGPRX2 activation. Currently, there is research for the development of small antagonists that will induce an anti-inflammatory effect by prevent [https://en.wikipedia.org/wiki/Immunoglobulin_E IgE-dependent] mast cell degranulation.<ref name="McNeil">McNeil, B. D., et al. "MRGPRX2 and Adverse Drug Reactions." Frontier Immunology, 06 August 2021, https://www.frontiersin.org/articles/10.3389/fimmu.2021.676354/full</ref> There are two antagonists that have been adapted from being agonists to another Class A GPCR, [https://en.wikipedia.org/wiki/NK1_receptor_antagonist neurokinin-1 receptor (NK-1R)].<ref name="Ogasawara">Ogasawara, H., et al. "Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells." Journal of Leukocyte Biology, 12 July 2019, https://jlb.onlinelibrary.wiley.com/doi/10.1002/JLB.2AB1018-405R</ref> Through the development of this research, these adverse side effects can be relieved and improve patient satisfaction.

Sandbox Reserved 1723: Difference between revisions

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@@ Line 77: / Line 77: @@
 [[Image:Zinc_and_drugs_snip.PNG|450px|right|thumb|'''Figure 6''': Structures of (R)-Zinc-3573, Dextromethorphan, Morphine, and Codeine. The blue circles indicate conserved basic N-dimethyl group and the green squares show the conserved benzene rings.<ref name="Cao"/>]]
-MRGPRX2 activation is associated with chronic itching or anaphylaxis reactions, a common side effect of many prescribed medications. <ref name="Cao"/> Among these drugs are opiods [https://en.wikipedia.org/wiki/Morphine morphine] and [https://en.wikipedia.org/wiki/Codeine codeine] and [https://en.wikipedia.org/wiki/Dextromethorphan dextromethorphan]. By analyzing the structures of these drugs, it can be seen that they contain chemical features similar to <scene name='90/904328/Zizwithaa/5'>agonist R-Zinc-3573</scene> (see Figure 6). They contain a conserved benzene ring that stabilizes them in binding pocket one (See Figure 6). Similarly, they contain an N-dimethyl group that would allow them to form key bonds with residues Asp-184 and Glu-164. Lastly, these drugs have a similar shape and size to that of the agonist R-Zinc-3573.<ref name="Babina"> Babina, M., et al. "MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through β-Arrestin and Lack of Correlation with the FcεRI Pathway." Journal of Investigative Dermatology, 141(6), 1286-1296. https://doi.org/10.1016/j.jid.2020.09.017</ref> These structural and chemical similarities indicate the possibility of a similar binding mechanism.
+MRGPRX2 activation is associated with chronic itching or anaphylaxis reactions, a common side effect of many prescribed medications. <ref name="Cao"/> Among these drugs are opiods [https://en.wikipedia.org/wiki/Morphine morphine] and [https://en.wikipedia.org/wiki/Codeine codeine] and [https://en.wikipedia.org/wiki/Dextromethorphan dextromethorphan]. By analyzing the structures of these drugs, it can be seen that they contain chemical features similar to <scene name='90/904328/Zizwithaa/5'>agonist R-Zinc-3573</scene> (see Figure 6). They contain a conserved benzene ring that stabilizes them in binding pocket one (see Figure 6). Similarly, they contain an N-dimethyl group that would allow them to form key bonds with residues Asp-184 and Glu-164. Lastly, these drugs have a similar shape and size to that of the agonist R-Zinc-3573.<ref name="Babina"> Babina, M., et al. "MRGPRX2 Is the Codeine Receptor of Human Skin Mast Cells: Desensitization through β-Arrestin and Lack of Correlation with the FcεRI Pathway." Journal of Investigative Dermatology, 141(6), 1286-1296. https://doi.org/10.1016/j.jid.2020.09.017</ref> These structural and chemical similarities indicate the possibility of a similar binding mechanism.
 This receptor is shallow and is able to bind to a variety of drugs, creating a need a solution to mediate the effects of MRGPRX2 activation. Currently, there is research for the development of small antagonists that will induce an anti-inflammatory effect by prevent [https://en.wikipedia.org/wiki/Immunoglobulin_E IgE-dependent] mast cell degranulation.<ref name="McNeil">McNeil, B. D., et al. "MRGPRX2 and Adverse Drug Reactions." Frontier Immunology, 06 August 2021, https://www.frontiersin.org/articles/10.3389/fimmu.2021.676354/full</ref> There are two antagonists that have been adapted from being agonists to another Class A GPCR, [https://en.wikipedia.org/wiki/NK1_receptor_antagonist neurokinin-1 receptor (NK-1R)].<ref name="Ogasawara">Ogasawara, H., et al. "Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells." Journal of Leukocyte Biology, 12 July 2019, https://jlb.onlinelibrary.wiley.com/doi/10.1002/JLB.2AB1018-405R</ref> Through the development of this research, these adverse side effects can be relieved and improve patient satisfaction.