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 language | English |
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Pages (from-to) | 12941-12945 |
Number of pages | 5 |
Journal | Journal of the American Chemical Society |
Volume | 132 |
Issue number | 37 |
DOIs | |
Publication status | Published - 2010 Sep 22 |
ASJC Scopus subject areas
- Catalysis
- Chemistry(all)
- Biochemistry
- Colloid and Surface Chemistry