Structure and biological evaluation of new cyclic and acyclic laxaphycin-A type peptides |
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Authors: | Louis Bornancin Eva Alonso Rebeca Alvariño Nicolas Inguimbert Isabelle Bonnard Luis M Botana Bernard Banaigs |
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Institution: | 1. PSL Research University, EPHE-UPVD-CNRS, USR 3278 CRIOBE, Université de Perpignan, 52 Avenue Paul Alduy, 66860 Perpignan Cedex, France;2. Laboratoire d’Excellence “CORAIL”, France;3. Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Campus de Lugo, Lugo 27002, Spain;4. Fundación Instituto de Investigación Sanitario Santiago de Compostela (FIDIS), Hospital Universitario Lucus Augusti, Lugo 27003, Spain |
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Abstract: | Five new laxaphycins were isolated and fully characterised from the bloom forming cyanobacteria Anabaena torulosa sampled from Moorea, French Polynesia: three acyclic laxaphycin A-type peptides, acyclolaxaphycin A (1), des-Gly11]acyclolaxaphycin A (2) and des-(Leu10-Gly11)]acyclolaxaphycin A (3), as well as two cyclic ones, l-Val8]laxaphycin A (4) and d-Val9]laxaphycin A (5). The absolute configuration of the amino acids, established using advanced Marfey’s analysis for compounds 2–5, highlights a conserved stereochemistry at the Cα carbons of the peptide ring that is characteristic of this family. To the best of our knowledge, this is the first report of acyclic analogues within the laxaphycin A-type peptides. Whether these linear laxaphycins with the aliphatic β-amino acid on the N-terminal are biosynthetic precursors or compounds obtained after enzymatic hydrolysis of the macrocycle is discussed. Biological evaluation of the new compounds together with the already known laxaphycin A shows that l-Val8]laxaphycin A, d-Val9]laxaphycin A and des-Gly11]acyclolaxaphycin induce cellular toxicity whereas laxaphycin A and des-(Leu10-Gly11)]acyclolaxaphycin A do not affect the cellular viability. An analysis of cellular death shows that the active peptides do not induce apoptosis or necrosis but instead, involve the autophagy pathway. |
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Keywords: | Corresponding author |
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