Abstract
A new peptaibol compound, SPF-5506-A4, was isolated from the fermentation broth of Trichoderma sp. SPF-5506. The chemical structure of the 14-residue peptide was determined by MS, NMR and amino acid sequence analyses. The absolute configuration of amino acid residues in the acid hydrolysate was determined by Marfey’s method. The structure of SPF-5506-A4 was established as Ac-Aib-L-Asn-L-Ile-Aib-L-Pro-L-Ser-L-Ile-Aib-L-Pro-L-Leu-L-Leu-Aib-L-Pro-L-leucinol. The compound inhibited amyloid β-peptide formation in primary guinea pig cerebral cortex neuron cell culture dose-dependently with an IC50 of 0.1 μg/ml. Cytotoxicity was not observed at concentrations of <3 μg/ml.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Whitmore L, Wallace BA . The peptaibol database: a database for sequences and structures of naturally occurring peptaibols. Nucleic Acids Res 32: 593–594 ( 2004)
Whitmore L, Wallace BA . Analysis of peptaibol sequence composition: implications for in vivo synthesis and channel formation. Eur Biophys J 33: 233–237 ( 2004)
Toniolo C, Crisma M, Formaggio F, Peggion C, Epand RF, Epand RM . Lipopeptaibols, a novel family of membrane active, antimicrobial peptides. Cell Mol Life Sci 58: 1179–1188 ( 2001)
Kim YH, Yeo WH, Kim YS, Chae SY, Kim KS . Antiviral activity of antibiotic peptaibols, chrysospemins B and D, produced by Apiocrea sp. 14T against TMV infection. J Microbiol Biotech 10: 522–528 ( 2000)
Leclerc G, Goulard C, Prigent Y, Bodo B, Wroblewski H, Rebuffat S . Sequences and antimycoplasmic properties of longibrachins LGB II and LGB III, two novel 20-residue peptaibols from Trichoderma longibrachiatum. J Nat Prod 64: 164–170 ( 2001)
He H, Janso JE, Yang HY, Bernan VS, Lin SL, Yu K . Culicinin D, an antitumor peptaibol produced by the fungus Culicinomyces clavisporus, strain LL-12I252. J Nat Prod 69: 736–741 ( 2006)
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K . Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82: 4245–4249 ( 1985)
Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, Larson E, L Lahad LL, Viitanen M, Peskind E, Poorkaj P, Schellenberg G, Tanzi R, Wasco W, Lannfelt L, Selkoe D, Younkin S . Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 2: 864–870 ( 1996)
Hardy J, Selkoe DJ . The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297: 353–356 ( 2002)
Rifai MA . A revision of the genus Trichoderma. Mycol Pap 116: 1–16 ( 1969)
Nippon Shikisai Kenkyuusyo . ( Ed.). Color Tone Manual. Nippon Shikiken Jigyo Co., Tokyo ( 1973)
Marfey P . Determination of D-amino acids. II. Use of a bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. Carlsberg Res Commun 49: 591–596 ( 1084)
Rebuffat S, Goulard C, Bodo B . Antibiotic peptides from Trichoderma harzianum: harzianins HC, proline-rich 14-residue peptaibols. J Chem Soc Perkin Trans 1 1995: 1849–1855 ( 1995)
Iida A, Sanekata M, Wada S, Fujita T, Tanaka H, Enoki A, Fuse G, Kanai M, Asami K . Fungal metabolites. XVIII. New membrane-modifying peptides, trichorozins I~IV, from the fungus Trichoderma harzianum. Chem Pharm Bull 43: 392–397 ( 1995)
Wada S, Iida A, Akimoto N, Kanai M, Toyama N, Fujita T . Fungal metabolites. XIX. Structural elucidation of channel-forming peptides, trichorovins-I~XIV, from the fungus Trichoderma viride. Chem Pharm Bull 43: 910–915 ( 1995)
Strooper BD, Konig G . Alzheimer's disease. A firm base for drug development. Nature 402: 471–472 ( 1999)
Sansom MSP . The biophysics of peptide models of ion channels. Prog Biophys Mol Biol 55: 139–235 ( 1991)
Woolley GA, Wallace BA . Model ion channels: gramicidin and alamethicin. J Membrane Biol 129: 109–136 ( 1992)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hosotani, N., Kumagai, K., Honda, S. et al. SPF-5506-A4, a New Peptaibol Inhibitor of Amyloid β-Peptide Formation Produced by Trichoderma sp.. J Antibiot 60, 184–190 (2007). https://doi.org/10.1038/ja.2007.20
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1038/ja.2007.20


