SPF-5506-A4, a new peptaibol inhibitor of amyloid beta-peptide formation produced by Trichoderma sp

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 beta-peptide formation in primary guinea pig cerebral cortex neuron cell culture dose-dependently with an IC50 of 0.1 microg/ml. Cytotoxicity was not observed at concentrations of <3 microg/ml.