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Solution Structure of Polytheonamide B, a Highly Cytotoxic Nonribosomal Polypeptide from Marine Sponge
Polytheonamide B (pTB), a highly cytotoxic polypeptide, is one of the most unusual nonribosomal peptides of sponge origin. pTB is a linear 48-residue peptide with alternating d- and l-amino acids and contains a total of eight types of nonproteinogenic amino acids. To investigate the mechanisms under...
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| Published in: | Journal of the American Chemical Society 2010-09, Vol.132 (37), p.12941-12945 |
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| Main Authors: | , , , , , , , |
| Format: | Article |
| Language: | English |
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| cites | cdi_FETCH-LOGICAL-a380t-31225ec54ff1db16c1f05a4aec8fdb438daaed49f2c57a84f4f0fae15da79c723 |
| container_end_page | 12945 |
| container_issue | 37 |
| container_start_page | 12941 |
| container_title | Journal of the American Chemical Society |
| container_volume | 132 |
| creator | Hamada, Toshiyuki Matsunaga, Shigeki Fujiwara, Masako Fujita, Kenichi Hirota, Hiroshi Schmucki, Roland Güntert, Peter Fusetani, Nobuhiro |
| description | Polytheonamide B (pTB), a highly cytotoxic polypeptide, is one of the most unusual nonribosomal peptides of sponge origin. pTB is a linear 48-residue peptide with alternating d- and l-amino acids and contains a total of eight types of nonproteinogenic amino acids. To investigate the mechanisms underlying its cytotoxic activity, we determined the three-dimensional structure of pTB by NMR spectroscopy, structure calculation, and energy minimization. pTB adopts a single right-handed β6.3-helical structure in a 1:1 mixture of methanol/chloroform with a length of approximately 45 Å and a hydrophilic pore of ca. 4 Å inner diameter. These features indicate that pTB molecules form transmembrane channels that permeate monovalent cations as gramicidin A channels do. The strong cytotoxicity of pTB can be ascribed to its ability to form single molecule channels through biological membranes. |
| doi_str_mv | 10.1021/ja104616z |
| format | article |
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To investigate the mechanisms underlying its cytotoxic activity, we determined the three-dimensional structure of pTB by NMR spectroscopy, structure calculation, and energy minimization. pTB adopts a single right-handed β6.3-helical structure in a 1:1 mixture of methanol/chloroform with a length of approximately 45 Å and a hydrophilic pore of ca. 4 Å inner diameter. These features indicate that pTB molecules form transmembrane channels that permeate monovalent cations as gramicidin A channels do. 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Am. Chem. Soc</addtitle><description>Polytheonamide B (pTB), a highly cytotoxic polypeptide, is one of the most unusual nonribosomal peptides of sponge origin. pTB is a linear 48-residue peptide with alternating d- and l-amino acids and contains a total of eight types of nonproteinogenic amino acids. To investigate the mechanisms underlying its cytotoxic activity, we determined the three-dimensional structure of pTB by NMR spectroscopy, structure calculation, and energy minimization. pTB adopts a single right-handed β6.3-helical structure in a 1:1 mixture of methanol/chloroform with a length of approximately 45 Å and a hydrophilic pore of ca. 4 Å inner diameter. These features indicate that pTB molecules form transmembrane channels that permeate monovalent cations as gramicidin A channels do. The strong cytotoxicity of pTB can be ascribed to its ability to form single molecule channels through biological membranes.</description><subject>Animals</subject><subject>Biomimetics</subject><subject>Cell Line, Tumor</subject><subject>Cell Membrane - metabolism</subject><subject>Inhibitory Concentration 50</subject><subject>Ion Channels - metabolism</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Organic Chemicals - chemistry</subject><subject>Peptides - chemistry</subject><subject>Peptides - metabolism</subject><subject>Peptides - pharmacology</subject><subject>Porifera - chemistry</subject><subject>Protein Conformation</subject><subject>Proteins - chemistry</subject><subject>Proteins - metabolism</subject><subject>Proteins - pharmacology</subject><subject>Solutions</subject><subject>Solvents - chemistry</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNptkF1LwzAUQIMobk4f_AOSFxHBapImbfeoQ50wP2D6XG7TZOtom5qkYP31dm7uyafLhXMP3IPQKSXXlDB6swJKeESj7z00pIKRQFAW7aMhIYQFcRKFA3Tk3KpfOUvoIRowEo9FxPgQ6bkpW1-YGs-9baVvrcJG4zdTdn6pTA1VkSt8d4UBT4vFsuzwpPPGm69C4hdT2yIzzlRQ_l40qvFrXFtT4WewRa3wvDH1Qh2jAw2lUyfbOUIfD_fvk2kwe318mtzOAggT4oOQMiaUFFxrmmc0klQTARyUTHSe8TDJAVTOx5pJEUPCNddEg6Iih3gsYxaO0MXG21jz2Srn06pwUpUl1Mq0Lo2FoNG6VU9ebkhpjXNW6bSxRQW2SylJ11XTXdWePdta26xS-Y78y9gD5xsApEtXprV1_-Q_oh_XEoBQ</recordid><startdate>20100922</startdate><enddate>20100922</enddate><creator>Hamada, Toshiyuki</creator><creator>Matsunaga, Shigeki</creator><creator>Fujiwara, Masako</creator><creator>Fujita, Kenichi</creator><creator>Hirota, Hiroshi</creator><creator>Schmucki, Roland</creator><creator>Güntert, Peter</creator><creator>Fusetani, Nobuhiro</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100922</creationdate><title>Solution Structure of Polytheonamide B, a Highly Cytotoxic Nonribosomal Polypeptide from Marine Sponge</title><author>Hamada, Toshiyuki ; Matsunaga, Shigeki ; Fujiwara, Masako ; Fujita, Kenichi ; Hirota, Hiroshi ; Schmucki, Roland ; Güntert, Peter ; Fusetani, Nobuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a380t-31225ec54ff1db16c1f05a4aec8fdb438daaed49f2c57a84f4f0fae15da79c723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Biomimetics</topic><topic>Cell Line, Tumor</topic><topic>Cell Membrane - metabolism</topic><topic>Inhibitory Concentration 50</topic><topic>Ion Channels - metabolism</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Organic Chemicals - chemistry</topic><topic>Peptides - chemistry</topic><topic>Peptides - metabolism</topic><topic>Peptides - pharmacology</topic><topic>Porifera - chemistry</topic><topic>Protein Conformation</topic><topic>Proteins - chemistry</topic><topic>Proteins - metabolism</topic><topic>Proteins - pharmacology</topic><topic>Solutions</topic><topic>Solvents - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hamada, Toshiyuki</creatorcontrib><creatorcontrib>Matsunaga, Shigeki</creatorcontrib><creatorcontrib>Fujiwara, Masako</creatorcontrib><creatorcontrib>Fujita, Kenichi</creatorcontrib><creatorcontrib>Hirota, Hiroshi</creatorcontrib><creatorcontrib>Schmucki, Roland</creatorcontrib><creatorcontrib>Güntert, Peter</creatorcontrib><creatorcontrib>Fusetani, Nobuhiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hamada, Toshiyuki</au><au>Matsunaga, Shigeki</au><au>Fujiwara, Masako</au><au>Fujita, Kenichi</au><au>Hirota, Hiroshi</au><au>Schmucki, Roland</au><au>Güntert, Peter</au><au>Fusetani, Nobuhiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Solution Structure of Polytheonamide B, a Highly Cytotoxic Nonribosomal Polypeptide from Marine Sponge</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2010-09-22</date><risdate>2010</risdate><volume>132</volume><issue>37</issue><spage>12941</spage><epage>12945</epage><pages>12941-12945</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Polytheonamide B (pTB), a highly cytotoxic polypeptide, is one of the most unusual nonribosomal peptides of sponge origin. pTB is a linear 48-residue peptide with alternating d- and l-amino acids and contains a total of eight types of nonproteinogenic amino acids. To investigate the mechanisms underlying its cytotoxic activity, we determined the three-dimensional structure of pTB by NMR spectroscopy, structure calculation, and energy minimization. pTB adopts a single right-handed β6.3-helical structure in a 1:1 mixture of methanol/chloroform with a length of approximately 45 Å and a hydrophilic pore of ca. 4 Å inner diameter. These features indicate that pTB molecules form transmembrane channels that permeate monovalent cations as gramicidin A channels do. The strong cytotoxicity of pTB can be ascribed to its ability to form single molecule channels through biological membranes.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>20795624</pmid><doi>10.1021/ja104616z</doi><tpages>5</tpages></addata></record> |
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| identifier | ISSN: 0002-7863 |
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| issn | 0002-7863 1520-5126 |
| language | eng |
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| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| subjects | Animals Biomimetics Cell Line, Tumor Cell Membrane - metabolism Inhibitory Concentration 50 Ion Channels - metabolism Mice Models, Molecular Nuclear Magnetic Resonance, Biomolecular Organic Chemicals - chemistry Peptides - chemistry Peptides - metabolism Peptides - pharmacology Porifera - chemistry Protein Conformation Proteins - chemistry Proteins - metabolism Proteins - pharmacology Solutions Solvents - chemistry |
| title | Solution Structure of Polytheonamide B, a Highly Cytotoxic Nonribosomal Polypeptide from Marine Sponge |
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