Solution structure of polytheonamide B, a highly cytotoxic nonribosomal polypeptide from marine sponge

Toshiyuki Hamada, Shigeki Matsunaga, Masako Fujiwara, Kenichi Fujita, Hiroshi Hirota, Roland Schmucki, Peter Güntert, Nobuhiro Fusetani

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49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)12941-12945
Number of pages5
JournalJournal of the American Chemical Society
Volume132
Issue number37
DOIs
Publication statusPublished - 2010 Sep 22

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Hamada, T., Matsunaga, S., Fujiwara, M., Fujita, K., Hirota, H., Schmucki, R., Güntert, P., & Fusetani, N. (2010). Solution structure of polytheonamide B, a highly cytotoxic nonribosomal polypeptide from marine sponge. Journal of the American Chemical Society, 132(37), 12941-12945. https://doi.org/10.1021/ja104616z