π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands
Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues a...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Du, Yu [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2024 |
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| Anmerkung: |
© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| Übergeordnetes Werk: |
Enthalten in: International journal of peptide research and therapeutics - Springer Netherlands, 2005, 30(2024), 2 vom: 10. März |
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| Übergeordnetes Werk: |
volume:30 ; year:2024 ; number:2 ; day:10 ; month:03 |
| Links: |
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| DOI / URN: |
10.1007/s10989-024-10596-9 |
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| Katalog-ID: |
SPR055091628 |
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| 520 | |a Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. | ||
| 650 | 4 | |a Tankyrase-1 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Inhibitor |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Aromatic amino acid |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a -stacking interaction |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Pentapeptide |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Molecular design |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Gynecologic tumor |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Xu, Lin |4 aut | |
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| 912 | |a GBV_ILN_2064 | ||
| 912 | |a GBV_ILN_2065 | ||
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10.1007/s10989-024-10596-9 doi (DE-627)SPR055091628 (SPR)s10989-024-10596-9-e DE-627 ger DE-627 rakwb eng 540 VZ 35.76 bkl Du, Yu verfasserin aut π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. Tankyrase-1 (dpeaa)DE-He213 Inhibitor (dpeaa)DE-He213 Aromatic amino acid (dpeaa)DE-He213 -stacking interaction (dpeaa)DE-He213 Pentapeptide (dpeaa)DE-He213 Molecular design (dpeaa)DE-He213 Gynecologic tumor (dpeaa)DE-He213 Xu, Lin aut Enthalten in International journal of peptide research and therapeutics Springer Netherlands, 2005 30(2024), 2 vom: 10. März Online-Ressource (DE-627)490716237 (DE-600)2192632-3 (DE-576)254902375 1573-3904 nnns volume:30 year:2024 number:2 day:10 month:03 https://dx.doi.org/10.1007/s10989-024-10596-9 lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.76 Aminosäuren Peptide Eiweiße Biochemie VZ AR 30 2024 2 10 03 |
| spelling |
10.1007/s10989-024-10596-9 doi (DE-627)SPR055091628 (SPR)s10989-024-10596-9-e DE-627 ger DE-627 rakwb eng 540 VZ 35.76 bkl Du, Yu verfasserin aut π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. Tankyrase-1 (dpeaa)DE-He213 Inhibitor (dpeaa)DE-He213 Aromatic amino acid (dpeaa)DE-He213 -stacking interaction (dpeaa)DE-He213 Pentapeptide (dpeaa)DE-He213 Molecular design (dpeaa)DE-He213 Gynecologic tumor (dpeaa)DE-He213 Xu, Lin aut Enthalten in International journal of peptide research and therapeutics Springer Netherlands, 2005 30(2024), 2 vom: 10. März Online-Ressource (DE-627)490716237 (DE-600)2192632-3 (DE-576)254902375 1573-3904 nnns volume:30 year:2024 number:2 day:10 month:03 https://dx.doi.org/10.1007/s10989-024-10596-9 lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.76 Aminosäuren Peptide Eiweiße Biochemie VZ AR 30 2024 2 10 03 |
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10.1007/s10989-024-10596-9 doi (DE-627)SPR055091628 (SPR)s10989-024-10596-9-e DE-627 ger DE-627 rakwb eng 540 VZ 35.76 bkl Du, Yu verfasserin aut π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. Tankyrase-1 (dpeaa)DE-He213 Inhibitor (dpeaa)DE-He213 Aromatic amino acid (dpeaa)DE-He213 -stacking interaction (dpeaa)DE-He213 Pentapeptide (dpeaa)DE-He213 Molecular design (dpeaa)DE-He213 Gynecologic tumor (dpeaa)DE-He213 Xu, Lin aut Enthalten in International journal of peptide research and therapeutics Springer Netherlands, 2005 30(2024), 2 vom: 10. März Online-Ressource (DE-627)490716237 (DE-600)2192632-3 (DE-576)254902375 1573-3904 nnns volume:30 year:2024 number:2 day:10 month:03 https://dx.doi.org/10.1007/s10989-024-10596-9 lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.76 Aminosäuren Peptide Eiweiße Biochemie VZ AR 30 2024 2 10 03 |
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10.1007/s10989-024-10596-9 doi (DE-627)SPR055091628 (SPR)s10989-024-10596-9-e DE-627 ger DE-627 rakwb eng 540 VZ 35.76 bkl Du, Yu verfasserin aut π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. Tankyrase-1 (dpeaa)DE-He213 Inhibitor (dpeaa)DE-He213 Aromatic amino acid (dpeaa)DE-He213 -stacking interaction (dpeaa)DE-He213 Pentapeptide (dpeaa)DE-He213 Molecular design (dpeaa)DE-He213 Gynecologic tumor (dpeaa)DE-He213 Xu, Lin aut Enthalten in International journal of peptide research and therapeutics Springer Netherlands, 2005 30(2024), 2 vom: 10. März Online-Ressource (DE-627)490716237 (DE-600)2192632-3 (DE-576)254902375 1573-3904 nnns volume:30 year:2024 number:2 day:10 month:03 https://dx.doi.org/10.1007/s10989-024-10596-9 lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.76 Aminosäuren Peptide Eiweiße Biochemie VZ AR 30 2024 2 10 03 |
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10.1007/s10989-024-10596-9 doi (DE-627)SPR055091628 (SPR)s10989-024-10596-9-e DE-627 ger DE-627 rakwb eng 540 VZ 35.76 bkl Du, Yu verfasserin aut π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. Tankyrase-1 (dpeaa)DE-He213 Inhibitor (dpeaa)DE-He213 Aromatic amino acid (dpeaa)DE-He213 -stacking interaction (dpeaa)DE-He213 Pentapeptide (dpeaa)DE-He213 Molecular design (dpeaa)DE-He213 Gynecologic tumor (dpeaa)DE-He213 Xu, Lin aut Enthalten in International journal of peptide research and therapeutics Springer Netherlands, 2005 30(2024), 2 vom: 10. März Online-Ressource (DE-627)490716237 (DE-600)2192632-3 (DE-576)254902375 1573-3904 nnns volume:30 year:2024 number:2 day:10 month:03 https://dx.doi.org/10.1007/s10989-024-10596-9 lizenzpflichtig Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 35.76 Aminosäuren Peptide Eiweiße Biochemie VZ AR 30 2024 2 10 03 |
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Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. 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Du, Yu ddc 540 bkl 35.76 misc Tankyrase-1 misc Inhibitor misc Aromatic amino acid misc -stacking interaction misc Pentapeptide misc Molecular design misc Gynecologic tumor π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands |
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π-stacking interactions involved in gynecologic tankyrase-1/inhibitor recognition and association: implications for rational design of aromatic pentapeptide ligands |
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π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands |
| abstract |
Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. © The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstractGer |
Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. © The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstract_unstemmed |
Abstract Human tankyrase-1 is an important regulator of poly(ADP-ribosyl)ation (PARylation) of Wnt/β-catenin signaling and has been recognized as a druggable target of gynecologic tumors. The active site of tankyrase-1 is rich with π-electron, which contains a number of aromatic amino aid residues and can form multiple π-stacking interactions with its substrates and ligands. In this study, computational analysis revealed that aromatic residues involved in tankyrase-1’s active site are significantly responsible for the intermolecular interaction between tankyrase-1 and its inhibitor ligands. Based on the harvested information, structure-based molecular design of aromatic pentapeptide inhibitors was carried out to target tankyrase-1. The pentapeptide candidates were defined by aromatic amino acids, and their π-stacking contribution is stronger than small-molecule inhibitors. Eight pentapeptide hits were determined to have moderate or high inhibitory potency against human tankyrase-1, in which two hits FYWYH and YWFYH can inhibit the enzyme potently at sub-micromolar level. Structural analysis observed a number of face-to-face, parallel-displaced and T-shaped π-stacking interactions at tankyrase-1/pentapeptide complex interface, which co-define a complicated π-stacking network and confer both stability and specificity for the complex formation. © The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| title_short |
π-Stacking Interactions Involved in Gynecologic Tankyrase-1/Inhibitor Recognition and Association: Implications for Rational Design of Aromatic Pentapeptide Ligands |
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https://dx.doi.org/10.1007/s10989-024-10596-9 |
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2024-07-04T04:08:00.627Z |
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| score |
7.4003267 |