Rational Design of a Modality‐Specific Inhibitor of TRPM8 Channel against Oxaliplatin‐Induced Cold Allodynia
Abstract Platinum‐based compounds in chemotherapy such as oxaliplatin often induce peripheral neuropathy and neuropathic pain such as cold allodynia in patients. Transient Receptor Potential Melastatin 8 (TRPM8) ion channel is a nociceptor critically involved in such pathological processes. Direct b...
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Wiley
2021
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oai:doaj.org-article:6708c24e19d8497b9799498ae01517f02021-11-17T08:40:31ZRational Design of a Modality‐Specific Inhibitor of TRPM8 Channel against Oxaliplatin‐Induced Cold Allodynia2198-384410.1002/advs.202101717https://doaj.org/article/6708c24e19d8497b9799498ae01517f02021-11-01T00:00:00Zhttps://doi.org/10.1002/advs.202101717https://doaj.org/toc/2198-3844Abstract Platinum‐based compounds in chemotherapy such as oxaliplatin often induce peripheral neuropathy and neuropathic pain such as cold allodynia in patients. Transient Receptor Potential Melastatin 8 (TRPM8) ion channel is a nociceptor critically involved in such pathological processes. Direct blockade of TRPM8 exhibits significant analgesic effects but also incurs severe side effects such as hypothermia. To selectively target TRPM8 channels against cold allodynia, a cyclic peptide DeC‐1.2 is de novo designed with the optimized hot‐spot centric approach. DeC‐1.2 modality specifically inhibited the ligand activation of TRPM8 but not the cold activation as measured in single‐channel patch clamp recordings. It is further demonstrated that DeC‐1.2 abolishes cold allodynia in oxaliplatin treated mice without altering body temperature, indicating DeC‐1.2 has the potential for further development as a novel analgesic against oxaliplatin‐induced neuropathic pain.Aerziguli AierkenYa‐Kai XieWenqi DongAbuliken ApaerJia‐Jia LinZihan ZhaoShilong YangZhen‐Zhong XuFan YangWileyarticledesigned proteinion channels, oxaliplatin‐induced cold allodyniapainTRPM8ScienceQENAdvanced Science, Vol 8, Iss 22, Pp n/a-n/a (2021) |
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designed protein ion channels, oxaliplatin‐induced cold allodynia pain TRPM8 Science Q |
| spellingShingle |
designed protein ion channels, oxaliplatin‐induced cold allodynia pain TRPM8 Science Q Aerziguli Aierken Ya‐Kai Xie Wenqi Dong Abuliken Apaer Jia‐Jia Lin Zihan Zhao Shilong Yang Zhen‐Zhong Xu Fan Yang Rational Design of a Modality‐Specific Inhibitor of TRPM8 Channel against Oxaliplatin‐Induced Cold Allodynia |
| description |
Abstract Platinum‐based compounds in chemotherapy such as oxaliplatin often induce peripheral neuropathy and neuropathic pain such as cold allodynia in patients. Transient Receptor Potential Melastatin 8 (TRPM8) ion channel is a nociceptor critically involved in such pathological processes. Direct blockade of TRPM8 exhibits significant analgesic effects but also incurs severe side effects such as hypothermia. To selectively target TRPM8 channels against cold allodynia, a cyclic peptide DeC‐1.2 is de novo designed with the optimized hot‐spot centric approach. DeC‐1.2 modality specifically inhibited the ligand activation of TRPM8 but not the cold activation as measured in single‐channel patch clamp recordings. It is further demonstrated that DeC‐1.2 abolishes cold allodynia in oxaliplatin treated mice without altering body temperature, indicating DeC‐1.2 has the potential for further development as a novel analgesic against oxaliplatin‐induced neuropathic pain. |
| format |
article |
| author |
Aerziguli Aierken Ya‐Kai Xie Wenqi Dong Abuliken Apaer Jia‐Jia Lin Zihan Zhao Shilong Yang Zhen‐Zhong Xu Fan Yang |
| author_facet |
Aerziguli Aierken Ya‐Kai Xie Wenqi Dong Abuliken Apaer Jia‐Jia Lin Zihan Zhao Shilong Yang Zhen‐Zhong Xu Fan Yang |
| author_sort |
Aerziguli Aierken |
| title |
Rational Design of a Modality‐Specific Inhibitor of TRPM8 Channel against Oxaliplatin‐Induced Cold Allodynia |
| title_short |
Rational Design of a Modality‐Specific Inhibitor of TRPM8 Channel against Oxaliplatin‐Induced Cold Allodynia |
| title_full |
Rational Design of a Modality‐Specific Inhibitor of TRPM8 Channel against Oxaliplatin‐Induced Cold Allodynia |
| title_fullStr |
Rational Design of a Modality‐Specific Inhibitor of TRPM8 Channel against Oxaliplatin‐Induced Cold Allodynia |
| title_full_unstemmed |
Rational Design of a Modality‐Specific Inhibitor of TRPM8 Channel against Oxaliplatin‐Induced Cold Allodynia |
| title_sort |
rational design of a modality‐specific inhibitor of trpm8 channel against oxaliplatin‐induced cold allodynia |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/6708c24e19d8497b9799498ae01517f0 |
| work_keys_str_mv |
AT aerziguliaierken rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia AT yakaixie rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia AT wenqidong rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia AT abulikenapaer rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia AT jiajialin rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia AT zihanzhao rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia AT shilongyang rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia AT zhenzhongxu rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia AT fanyang rationaldesignofamodalityspecificinhibitoroftrpm8channelagainstoxaliplatininducedcoldallodynia |
| _version_ |
1718425675555143680 |