Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933
Chemical investigation of the psychrophilic fungus Pseudogymnoascus sp. HDN17-933 derived from Antarctica led to the discovery of six new tetrapeptides psegymamides A–F (1–6), whose planar structures were elucidated by extensive NMR and MS spectrometric analyses. Structurally, psegymamides D–F (4–6)...
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ftpubmed:oai:pubmedcentral.nih.gov:9604729 2023-05-15T14:01:20+02:00 Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933 Hou, Xuewen Li, Changlong Zhang, Runfang Li, Yinping Li, Huadong Zhang, Yundong Tae, Han-Shen Yu, Rilei Che, Qian Zhu, Tianjiao Li, Dehai Zhang, Guojian 2022-09-22 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604729/ http://www.ncbi.nlm.nih.gov/pubmed/36286417 https://doi.org/10.3390/md20100593 en eng MDPI http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604729/ http://www.ncbi.nlm.nih.gov/pubmed/36286417 http://dx.doi.org/10.3390/md20100593 © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). CC-BY Mar Drugs Article Text 2022 ftpubmed https://doi.org/10.3390/md20100593 2022-10-30T01:14:10Z Chemical investigation of the psychrophilic fungus Pseudogymnoascus sp. HDN17-933 derived from Antarctica led to the discovery of six new tetrapeptides psegymamides A–F (1–6), whose planar structures were elucidated by extensive NMR and MS spectrometric analyses. Structurally, psegymamides D–F (4–6) possess unique backbones bearing a tetrahydropyridoindoles unit, which make them the first examples discovered in naturally occurring peptides. The absolute configurations of structures were unambiguously determined using solid-phase total synthesis assisted by Marfey’s method, and all compounds were evaluated for their inhibition of human (h) nicotinic acetylcholine receptor subtypes. Compound 2 showed significant inhibitory activity. A preliminary structure–activity relationship investigation revealed that the tryptophan residue and the C-terminal with methoxy group were important to the inhibitory activity. Further, the high binding affinity of compound 2 to hα4β2 was explained by molecular docking studies. Text Antarc* Antarctica PubMed Central (PMC) Marine Drugs 20 10 593 |
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Article Hou, Xuewen Li, Changlong Zhang, Runfang Li, Yinping Li, Huadong Zhang, Yundong Tae, Han-Shen Yu, Rilei Che, Qian Zhu, Tianjiao Li, Dehai Zhang, Guojian Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933 |
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Article |
description |
Chemical investigation of the psychrophilic fungus Pseudogymnoascus sp. HDN17-933 derived from Antarctica led to the discovery of six new tetrapeptides psegymamides A–F (1–6), whose planar structures were elucidated by extensive NMR and MS spectrometric analyses. Structurally, psegymamides D–F (4–6) possess unique backbones bearing a tetrahydropyridoindoles unit, which make them the first examples discovered in naturally occurring peptides. The absolute configurations of structures were unambiguously determined using solid-phase total synthesis assisted by Marfey’s method, and all compounds were evaluated for their inhibition of human (h) nicotinic acetylcholine receptor subtypes. Compound 2 showed significant inhibitory activity. A preliminary structure–activity relationship investigation revealed that the tryptophan residue and the C-terminal with methoxy group were important to the inhibitory activity. Further, the high binding affinity of compound 2 to hα4β2 was explained by molecular docking studies. |
format |
Text |
author |
Hou, Xuewen Li, Changlong Zhang, Runfang Li, Yinping Li, Huadong Zhang, Yundong Tae, Han-Shen Yu, Rilei Che, Qian Zhu, Tianjiao Li, Dehai Zhang, Guojian |
author_facet |
Hou, Xuewen Li, Changlong Zhang, Runfang Li, Yinping Li, Huadong Zhang, Yundong Tae, Han-Shen Yu, Rilei Che, Qian Zhu, Tianjiao Li, Dehai Zhang, Guojian |
author_sort |
Hou, Xuewen |
title |
Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933 |
title_short |
Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933 |
title_full |
Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933 |
title_fullStr |
Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933 |
title_full_unstemmed |
Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933 |
title_sort |
unusual tetrahydropyridoindole-containing tetrapeptides with human nicotinic acetylcholine receptors targeting activity discovered from antarctica-derived psychrophilic pseudogymnoascus sp. hdn17-933 |
publisher |
MDPI |
publishDate |
2022 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604729/ http://www.ncbi.nlm.nih.gov/pubmed/36286417 https://doi.org/10.3390/md20100593 |
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Antarc* Antarctica |
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Antarc* Antarctica |
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Mar Drugs |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604729/ http://www.ncbi.nlm.nih.gov/pubmed/36286417 http://dx.doi.org/10.3390/md20100593 |
op_rights |
© 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
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CC-BY |
op_doi |
https://doi.org/10.3390/md20100593 |
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Marine Drugs |
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20 |
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