کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1177795 | 962610 | 2015 | 8 صفحه PDF | دانلود رایگان |
• Successful solid phase synthesis of 14-residue Trichoderma peptaibol SPF-5506-A4.
• Solution NMR reveals β-bend ribbon spiral core structure with flexible termini.
• SPF-5506-A4 shows low hemolytic activity and preferentially binds anionic membranes.
• The peptaibol forms large (> 4.6 nm) non-lytic pores in the membrane.
• SPF-5506-A4 follows the toroidal pore model in its mode of action.
The medium-length fungal peptaibol SPF-5506-A4 has been shown to inhibit formation of the Aβ peptide involved in Alzheimer'’s disease. As Aβ is a cleavage-product from the membrane-bound APP protein, we hypothesized that SPF-5506-A4's activity might be linked to membrane interactions in general. Here we describe the synthesis, structure and membrane interactions of SPF-5506-A4. The challenging synthesis was carried out on solid phase and a detailed conformational analysis in solution revealed a β-bend ribbon spiral core structure with flexible termini. Investigations of its membrane activity revealed low hemolytic activity, limited inhibition of both Gram-positive and Gram-negative cell growth and a preference for an overall negatively charged membrane surface mimicking the bacterial cell surface. SPF-5506-A4 is the first peptaibol to be shown to facilitate leakage of large (4.6 nm diameter) fluorescence-labeled dextran from vesicles while leaving the vesicles intact. We conclude that SPF-5506-A4 follows the toroidal pore model in its mode of action.
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Journal: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics - Volume 1854, Issue 8, August 2015, Pages 882–889