Solution Structure of Polytheonamide B, a Highly Cytotoxic Nonribosomal Polypeptide from Marine Sponge
- 26 August 2010
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 132 (37), 12941-12945
- https://doi.org/10.1021/ja104616z
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.Keywords
This publication has 34 references indexed in Scilit:
- Marine natural productsNatural Product Reports, 2010
- Gramicidin ChannelsIEEE Transactions on Nanobioscience, 2005
- Polytheonamides A and B, Highly Cytotoxic, Linear Polypeptides with Unprecedented Structural Features, from the Marine Sponge,TheonellaswinhoeiJournal of the American Chemical Society, 2004
- Nonribosomal Peptides from Marine SpongesCurrent Organic Chemistry, 2003
- [A channel-forming peptide toxin: polytheonamide from marine sponge (Theonella swinhoei)].Folia Pharmacologica Japonica, 1997
- A Nonribosomal System of Peptide BiosynthesisEuropean Journal of Biochemistry, 1996
- Voltage-dependent gating of an asymmetric gramicidin channel.Proceedings of the National Academy of Sciences of the United States of America, 1995
- Polytheonamides, unprecedented highly cytotoxic polypeptides, from the marine sponge theonella swinhoei: 1. Isolation and component amino acidsTetrahedron Letters, 1994
- Polytheonamides, unprecedented highly cytotoxic polypeptides from the marine sponge Theonella swinhoei 2. Structure elucidationTetrahedron Letters, 1994
- Bioactive sponge peptidesChemical Reviews, 1993